DNA- och proteinkartläggning samt behandlingseffekter i relation till tidigt åldrande vid Turners syndrom (TS) - mortalitet, morbiditet och fertilitet.
DNA- och proteinkartläggning samt behandlingseffekter i relation till tidigt åldrande vid Turners syndrom (TS) - mortalitet, morbiditet och fertilitet.
Project number : 3586
Created by: Inger Bryman, 2008-03-12
Last revised by: Inger Bryman, 2011-04-05
Project created in: FoU i Västra Götalandsregionen


1. Översiktlig projektbeskrivning

Engelsk titel

DNA and protein mapping and outcome of medical treatment in relation to early aging in Turner's syndrome (TS) - mortality, morbidity and fertility aspects.

Populärvetenskaplig sammanfattning av projektet

Projektsammanfattning (svensk och engelsk)
Vi studerar TS som modell för åldersrelaterade sjukdomar för att finna orsakssamband, riskfaktorer och prognostiska faktorer som även kan gälla för normalbefolkningen.
Vår hypotes är:
1. Den stora fenotypiska variation som ses vid Turners syndrom (TS) trots gemensam karyotyp (45X) förklaras av olikheter i genomets metyleringsmönster och påverkan på cellcykeln.
2. Individuellt anpassad hormon behandling ger bättre hälsa, livskvalitet och ökad överlevnad vid TS.
Trots samma genotyp ses stor individuell variation i stigmata och sjuklighet relaterad till ålderssjukdomar som hjärtkärlsjukdom (hypertoni, aortadiss), hörselnedsättning, osteoporos, gonadinsufficiens och cancer. Vi skall med molekylärbiologisk metodik (epigenetik/genetik samt proteomics) studera detta, nu mer detaljrikt än gennivån. I nationellt och internationellt samarbete har vi den bäst kartlagda TS-population som finns vad gäller fenotyp/genotyp i olika åldersgrupper och med olika behandlingsbakgrund. Därtill unika populationsbaserade kontrollmaterial för somatiska, psykosociala samt audiologisk data, samt tillgång till folkhälsoregister för jämförelser. Utöver tvärsnitts- och longitudinella data (10 år) har vi tillskapat "Svenskt genetiskt Turnerregister" (700 kvinnor). Vi saknar långtidsuppföljning av morbiditet, mortalitet och effekter av modern behandling med GH och könssteroider, liksom kontrollerade studier av graviditet och hälsan hos födda barn. För tidig död i aortadissektion beskrivs även under graviditet liksom ökad risk för andra komplikationer.

We study TS as a model for age related diseases to find background factors, risk- and prognostic factors which can also be applied to the normal population.

Our hypothesis is that
1.the variation of fenotype which is found in Turner Syndrom (TS) in spite of identical karyotype (45,X) could be explained by differences in pattern of methylation in the genome and effects on the cellcycle.
hormone treatment which is individually adjusted could contribute to better health, life quality and increased life expectancy for TS women. In spite of the same genotype a large individual variation of stigmata and health correlated to agespecific diseases like cardiovascular problems (hypertension, dissection of aortae), osteoporosis, insufficient gonad function and cancer is found. With the use of molecular technique (epigenetics/genetics and proteomics) we intend to study this relation more in detail. In a national and international network and co-operation we have obtained the best described TS population concerning fenotype/genotype with different age groups and different treatments. For comparison we also have access to unique populationbased control groups with data concerning somatic and psychosocial health from the Swedish population. Crossectional and longitudinal data (10 years) have been used for establishment of ”Swedish Genetic Turner Register” (700 women). There is still a lack of longitudinal studies concerning morbidity and mortality and effects of modern treatment with GH and steroids as well as controlled studies of pregnancy and health of newborn children. Death at young age in dissection of the aortae has been described even during pregnancy as well as increased risk for other pregnancy complications.

Typ av projekt


MeSH-termer för att beskriva typ av studier

checked Hälso- och sjukvårdsundersökningar (Health Care Surveys)
checked Longitudinella studier (Longitudinal Studies)
checked Retrospektiva studier (Retrospective Studies)
checked Fall-kontrollstudier (Case-Control Studies)
checked Kohortstudier (Cohort Studies)
checked Tvärsnittsstudier (Cross-Sectional Studies)

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MeSH-termer för att beskriva ämnesområdet

information Added MeSH terms
Congenital Abnormalities
Malformations of organs or body parts during development in utero.
Abortion, Therapeutic
Abortion induced to save the life or health of a pregnant woman. (From Dorland, 28th ed)
Acute Disease
Disease having a short and relatively severe course.
Adaptation, Psychological
A state of harmony between internal needs and external demands and the processes used in achieving this condition. (From APA Thesaurus of Psychological Index Terms, 8th ed)
A person 13 to 18 years of age.
A person having attained full growth or maturity. Adults are of 19 through 44 years of age.
Age Factors
Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.
A person 65 through 79 years of age. For a person older than 79 years, AGED, 80 AND OVER is available.
Aged, 80 and over
A person 80 years of age and older.
Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
Aneurysm, Dissecting
Aneurysm caused by a tear in the TUNICA INTIMA of a blood vessel leading to interstitial HEMORRHAGE, and splitting (dissecting) of the vessel wall, often involving the AORTA. Dissection between the intima and media causes luminal occlusion. Dissection at the media, or between the media and the outer adventitia causes aneurismal dilation.
An enduring, learned predisposition to behave in a consistent way toward a given class of objects, or a persistent mental and/or neural state of readiness to react to a certain class of objects, not as they are but as they are conceived to be.
Attitude to Health
Public attitudes toward health, disease, and the medical care system.
The testing of the acuity of the sense of hearing to determine the thresholds of the lowest intensity levels at which an individual can hear a set of tones. The frequencies between 125 and 8000 Hz are used to test air conduction thresholds and the frequencies between 250 and 4000 Hz are used to test bone conduction thresholds.
Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.
Blood Pressure
Body Composition
The relative amounts of various components in the body, such as percent body fat.
Body Height
The distance from the sole to the crown of the head with body standing on a flat surface and fully extended.
Body Image
Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects.
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.
A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL.
Child Development
The continuous sequential physiological and psychological maturing of an individual from birth up to but not including ADOLESCENCE.
Child, Preschool
A child between the ages of 2 and 5.
The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.
Chromosome Deletion
Actual loss of a portion of the chromosome.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)
Consumer Satisfaction
Customer satisfaction or dissatisfaction with a benefit or service received.
Description missing
Diabetes Mellitus
A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.
Diagnosis, Differential
Determination of which one of two or more diseases or conditions a patient is suffering from by systematically comparing and contrasting results of diagnostic measures.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Drug Therapy, Combination
Therapy with two or more separate preparations given for a combined effect.
The hearing and equilibrium system of the body. It consists of three parts: the EXTERNAL EAR, the MIDDLE EAR, and the INNER EAR. Sound waves are transmitted through this organ where vibration is transduced to nerve signals that pass through the ACOUSTIC NERVE to the CENTRAL NERVOUS SYSTEM. The inner ear also contains the vestibular organ that maintains equilibrium by transducing signals to the VESTIBULAR NERVE.
Ear Diseases
Pathological processes of the ear, the hearing, and the equilibrium system of the body.
Ear, External
The outer part of the hearing system of the body. It includes the shell-like EAR AURICLE which collects sound, and the EXTERNAL EAR CANAL, the TYMPANIC MEMBRANE, and the EXTERNAL EAR CARTILAGES.
Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic.
Ethinyl Estradiol
A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.
A social group consisting of parents or parent substitutes and children.
Male parents, human or animal.
Description missing
Fertilization in Vitro
An assisted reproductive technique that includes the direct handling and manipulation of oocytes and sperm to achieve fertilization in vitro.
Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.
Follow-Up Studies
Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.
Follicle Stimulating Hormone
A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.
Gender Identity
A person's concept of self as being male and masculine or female and feminine, or ambivalent, based in part on physical characteristics, parental responses, and psychological and social pressures. It is the internal experience of gender role.
The genetic constitution of the individual; the characterization of the genes.
Gradual increase in the number, the size, and the complexity of cells of an individual. Growth generally results in increase in ORGAN WEIGHT; BODY WEIGHT; and BODY HEIGHT.
Health Education
Education that increases the awareness and favorably influences the attitudes and knowledge relating to the improvement of health on a personal or community basis.
Health Services Needs and Demand
Health services required by a population or community as well as the health services that the population or community is able and willing to pay for.
Health Status
The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures.
The sensation of sound.
Hearing Disorders
Conditions that impair the transmission of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways.
Hearing Loss, Conductive
Hearing loss due to interference with the mechanical reception or amplification of sound to the COCHLEA. The interference is in the outer or middle ear involving the EAR CANAL; TYMPANIC MEMBRANE; or EAR OSSICLES.
Hearing Loss, Sensorineural
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.
Heart Defects, Congenital
Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.
Members of the species Homo sapiens.
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.
A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.
A child between 1 and 23 months of age.
Infant, Newborn
An infant during the first month after birth.
Infertility, Female
Diminished or absent ability of a female to achieve conception.
Information Services
Organized services to provide information on any questions an individual might have using databases and other sources. (From Random House Unabridged Dictionary, 2d ed)
Insulin-Like Growth Factor I
A well-characterized basic peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like, and mitogenic activities. This growth factor has a major, but not absolute, dependence on GROWTH HORMONE. It is believed to be mainly active in adults in contrast to INSULIN-LIKE GROWTH FACTOR II, which is a major fetal growth factor.
Interviews as Topic
Conversations with an individual or individuals held in order to obtain information about their background and other personal biographical data, their attitudes and opinions, etc. It includes school admission or job interviews.
Iodide Peroxidase
A hemeprotein that catalyzes the oxidation of the iodide radical to iodine with the subsequent iodination of many organic compounds, particularly proteins. EC
Mapping of the full chromosome set of the nucleus of a cell. The chromosome characteristics of an individual or a cell line are usually presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. (From Stedman, 25th ed)
Life Style
Typical way of life or manner of living characteristic of an individual or group. (From APA, Thesaurus of Psychological Index Terms, 8th ed)
A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells.
Description missing
Middle Aged
Description missing
The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1.
The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single ZYGOTE, as opposed to CHIMERISM in which the different cell populations are derived from more than one zygote.
Female parents, human or animal.
Mouth Mucosa
Lining of the ORAL CAVITY, including mucosa on the GUMS; the PALATE; the LIP; the CHEEK; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous EPITHELIUM covering muscle, bone, or glands but can show varying degree of keratinization at specific locations.
Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.
Otitis Media
Inflammation of the MIDDLE EAR including the AUDITORY OSSICLES and the EUSTACHIAN TUBE.
The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.
A synthetic hormone with anabolic and androgenic properties.
Parathyroid Hormone
A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.
Persons functioning as natural, adoptive, or substitute parents. The heading includes the concept of parenthood as well as preparation for becoming a parent.
Behavior-response patterns that characterize the individual.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
A period in the human life in which the development of the hypothalamic-pituitary-gonadal system takes place and reaches full maturity. The onset of synchronized endocrine events in puberty lead to the capacity for reproduction (FERTILITY), development of secondary SEX CHARACTERISTICS, and other changes seen in ADOLESCENT DEVELOPMENT.
Quality of Life
A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment; the overall condition of a human life.
Predetermined sets of questions used to collect data - clinical data, social status, occupational group, etc. The term is often applied to a self-completed survey instrument.
Receptors, Androgen
Proteins, generally found in the cytoplasm, that specifically bind androgens and mediate their cellular actions. The complex of the androgen and receptor migrates to the nucleus where it induces transcription of specific segments of DNA.
The return of a sign, symptom, or disease after a remission.
Reference Values
The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.
Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)
The probability that an event will occur. It encompasses a variety of measures of the probability of a generally unfavorable outcome.
Risk Factors
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
Self Assessment (Psychology)
Appraisal of one's own personal qualities or traits.
Self Concept
A person's view of himself.
Severity of Illness Index
Levels of severity of illness within a diagnostic group which are established by various measurement criteria.
Sex Hormone-Binding Globulin
A glycoprotein migrating as a beta-globulin. Its molecular weight, 52,000 or 95,000-115,000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as ANDROGEN-BINDING PROTEIN. They differ by their sites of synthesis and post-translational oligosaccharide modifications.
Gonadal Steroid Hormones
Steroid hormones produced by the GONADS. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include ESTRADIOL; PROGESTERONE; and TESTOSTERONE.
Social Adjustment
Adaptation of the person to the social environment. Adjustment may take place by adapting the self to the environment or by changing the environment. (From Campbell, Psychiatric Dictionary, 1996)
Social Behavior
Any behavior caused by or affecting another individual, usually of the same species.
Social Isolation
The separation of individuals or groups resulting in the lack of or minimizing of social contact and/or communication. This separation may be accomplished by physical separation, by social barriers and by psychological mechanisms. In the latter, there may be interaction but no real communication.
Social Support
Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc.
Socioeconomic Factors
Social and economic factors that characterize the individual or group within the social structure.
Somatoform Disorders
Disorders having the presence of physical symptoms that suggest a general medical condition but that are not fully explained by a general medical condition, by the direct effects of a substance, or by another mental disorder. The symptoms must cause clinically significant distress or impairment in social, occupational, or other areas of functioning. In contrast to FACTITIOUS DISORDERS and MALINGERING, the physical symptoms are not under voluntary control. (APA, DSM-IV)
Growth Hormone
A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized.
Communication through a system of conventional vocal symbols.
Description missing
A glycoprotein hormone secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Thyrotropin stimulates THYROID GLAND by increasing the iodide transport, synthesis and release of thyroid hormones (THYROXINE and TRIIODOTHYRONINE). Thyrotropin consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the pituitary glycoprotein hormones (TSH; LUTEINIZING HORMONE and FSH), but the beta subunit is unique and confers its biological specificity.
Turner Syndrome
A syndrome of defective gonadal development in phenotypic women with a karyotype of sex chromosome monosomy (45,X or 45,XO), associated with the loss of a sex chromosome X or Y. Patients generally are of short stature with undifferentiated (streak) gonads, sexual infantilism (HYPOGONADISM), webbing of the neck, cubitus valgus, elevated GONADOTROPINS and decreased ESTRADIOL level in blood. Studies of Turner Syndrome and its variants have contributed significantly to the understanding of SEX DIFFERENTIATION. NOONAN SYNDROME bears similarity to this disorder; however, it also occurs in males, has normal karyotype, and is inherited as an autosomal dominant.
Tympanic Membrane
An oval semitransparent membrane separating the external EAR CANAL from the tympanic cavity (EAR, MIDDLE). It contains three layers: the skin of the external ear canal; the core of radially and circularly arranged collagen fibers; and the MUCOSA of the middle ear.
The sounds produced by humans by the passage of air through the LARYNX and over the VOCAL CORDS, and then modified by the resonance organs, the NASOPHARYNX, and the MOUTH.
Voice Quality
That component of SPEECH which gives the primary distinction to a given speaker's VOICE when pitch and loudness are excluded. It involves both phonatory and resonatory characteristics. Some of the descriptions of voice quality are harshness, breathiness and nasality.
X Chromosome
The female sex chromosome, being the differential sex chromosome carried by half the male gametes and all female gametes in human and other male-heterogametic species.
Y Chromosome
The male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans and in some other male-heterogametic species in which the homologue of the X chromosome has been retained.
Bone Density
The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.
Vitamin K-dependent calcium-binding protein synthesized by OSTEOBLASTS and found primarily in BONES. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of CALCIUM, promotes binding to HYDROXYAPATITE and subsequent accumulation in BONE MATRIX.
Estrogen Replacement Therapy
The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, DYSPAREUNIA, and progressive development of OSTEOPOROSIS. This may also include the use of progestational agents in combination therapy.
Body Mass Index
An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)
The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.
Survival Rate
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
Chi-Square Distribution
A distribution in which a variable is distributed like the sum of the squares of any given independent random variable, each of which has a normal distribution with mean of zero and variance of one. The chi-square test is a statistical test based on comparison of a test statistic to a chi-square distribution. The oldest of these tests are used to detect whether two or more population distributions differ from one another.
Polymerase Chain Reaction
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
In Situ Hybridization, Fluorescence
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Aortic Aneurysm, Thoracic
An abnormal balloon- or sac-like dilatation in the wall of the THORACIC AORTA. This proximal descending portion of aorta gives rise to the visceral and the parietal branches above the aortic hiatus at the diaphragm.
Oocyte Donation
Transfer of preovulatory oocytes from donor to a suitable host. Oocytes are collected, fertilized in vitro, and transferred to a host that can be human or animal.
Trinucleotide Repeats
Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.
Disabled Children
Children with mental or physical disabilities that interfere with usual activities of daily living and that may require accommodation or intervention.
Hormone Replacement Therapy
Therapeutic use of hormones to alleviate the effects of hormone deficiency.
Chromosomes, Human, Y
The human male sex chromosome, being the differential sex chromosome carried by half the male gametes and none of the female gametes in humans.
Waist-Hip Ratio
The waist circumference measurement divided by the hip circumference measurement. For both men and women, a waist-to-hip ratio (WHR) of 1.0 or higher is considered "at risk" for undesirable health consequences, such as heart disease and ailments associated with OVERWEIGHT. A healthy WHR is 0.90 or less for men, and 0.80 or less for women. (National Center for Chronic Disease Prevention and Health Promotion, 2004)
Fractures, Bone
Breaks in bones.

Projektets delaktighet i utbildning

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2. Projektorganisation och finansiering

Arbetsplatser involverade i projektet

information Added workplaces
Landsting - Västra Götalandsregionen - Specialiserad vård - Sahlgrenska Universitetssjukhuset - Område 1 - Övrigt


Ulla-Britt Wennerholm
Universitetssjukhusöverläkare, Kvinnosjukvård, Institutionen för kliniska vetenskaper
Per Olof Janson
Professor emeritus, Avd för Ob/Gyn, SU/SS
Kerstin Landin Wilhelmsen
Professor Överläkare, Medicin, Sahlgrenska, Göteborgs universitetsbibliotek
Marie-Louise Barrenäs
Överläkare, Docent, Institutionen för kliniska vetenskaper, Neuro-huvud-halscentrum Västerbotten
Ulla Wide
leg psykolog, Institutionen för odontologi, Specialisttandvård
Anders Möller
Forskningschef/professor, Bräcke Diakoni
Mostafa ELmansoury
leg läk, Med klin, Sahlgrenska Universitetssjukhuset/Ö
Charles Hanson
Docent, Kvinnosjukvård
Emily Krantz
Specialistläkare internmedicin, Södra Älvsborgs sjukhus (SÄS)
Ann-Christine Ohlsson
Logoped, Område 5, Institutionen för medicin
Heidrun Kjellberg
Övertandläkare, docent, Göteborg
Sara Rizell
Övertandläkare, Specialisttandvård
Gunnel Andersson Wallgren
Leg logoped, Centrum för pediatrisk tillväxtforskning, Drottning Silvias barn- och ungdomssjukhus, SU/Östra
Hannah Park
Biolog, Kvinnosjukvård
Annika Reims
Överläkare, Barnmedicin

3. Processen och projektets redovisning

Hur långt har projektet framskridit?

Rekrytering/datainsamling pågår

Projektstart (när planeringen påbörjas och börjar dokumenteras skriftligt)


Datum då projektet är slutrapporterat


Publikationer från detta projekt

  1. Gravholt CH, Landin-Wilhelmsen K, Stochholm K, Hjerrild BE, Ledet T, Djurhuus CB, Sylvén L, Baandrup U, Kristensen BØ, Christiansen JS.
    Cardiol Young 2006:16(5):430-6.
  2. Boman UW, Hanson C, Hjelmquist E, Möller A.
    Scand J Psychol 2006:47(3):219-23.
  3. Landin Wilhelmsen K, El-Mansoury M, Bryman I, Berntorp K, Hanson C, Wilhelmsen L.
    Elsevier Publishing; 2006, pp 6.
  4. Starke M, Albertsson-Wikland K, Bäck-Wiklund M, Möller A.
    Journal of paediatrics and child health 2003:39
  5. Starke M, Albertsson-Wikland K, Bäck-Wiklund M, Möller A.
    Patient education and counseling 2002:47
  6. Boman UW, Bryman I, Halling K, Möller A.
    J Psychosom Obstet Gynaecol 2001:22(2):113-22.
  7. Saenger P, Albertsson-Wikland K, Conway G, Davenport M, Gravholt C, Hintz R, Hovatta O, Hultcrantz M, Landin Wilhelmsen K, Lin A, Lippe B, Pasquino A, Ranke M, Pasenfield R, Silberbach M.
    The Journal of clinical endocrinology and metabolism 2001:86
  8. Wide Boman U, Bryman I, Möller A, Hanson C.
    European journal of human genetics : EJHG 2001:9
  9. Landin-Wilhelmsen K, Bryman I, Windh M, Wilhelmsen L.
    Clin Endocrinol (Oxf) 1999:51(4):497-502.
  10. Stenberg AE, Nylén O, Windh M, Hultcrantz M.
    Hear Res. 1998:124(1-2):85-90.
  11. J Psychosom Obstet Gynaecol 1998:19(1):1-18.
  12. Westlander G, Janson PO, Tägnfors U, Bergh C.
    Acta Obstet Gynecol Scand 1998:77(3):317-21.
  13. Hamberger L H, Hanson C.
    Microscopy of Reproduction and Development Adynamic approach. Italy: Antonio Delfino Editore; 1997, pp 3.

Detaljerad projektbeskrivning


TS kan utgöra en modell för studier av åldrandets sjukdomar. Våra in silico studier av microarray-data på mus med TS (GEO database/GSE 1606) visar en uppreglering av det nätverk som reglerar apoptos och cellcykel via p53 genen och som även innefattar CDKN1A och CDKN2A genen hos mus med maternell X-kromosom. Hos mus med paternell X-kromosom är nätverket nedreglerat. I det fall omregleringen innebär ett ökat behov av p53 expression i form av en ökad broms på cellcykeln torde detta innebära en nedsatt förmåga i vävnaden att ersätta cellförlust pga apoptos. Detta kan leda till ett tidigare och mer uttalat åldrande jämfört med vävnad som lättare ersätter en cellförlust. Den mycket stora individuella variationen av stigmata och morbiditet inom samma TS genotyp 45X med maternell respektive paternell X-kromosom gör att vi med hjälp av DNA micro-array teknik kan studera genomets variation i metyleringsmönster, vilket kan relateras till sjukdomsbild och funktion (11-13). Proteomics ger förutsättning för identifikation av aktuella geners proteinprodukt. En avvikande proteinhalt eller proteinstruktur ger oss viktig information om uppkomstmekanismerna bakom de komplikationer som förekommer vid TS.
Diagnosen TS grundas på frånvaro av ena X-kromosomen i alla (45X) eller en del av kroppens celler (45X/46XX) alt olika strukturella kromosomavvikelser (1-2). Samband mellan karyotyp och fenotyp vid TS har med cytogenetik endast påvisats i begränsad omfattning (14-15). Våra studier har med fluorescens in situ hybridisering (FISH) visat att mosaicism (45X/46XX) lindrar TS fenotypen. Detta gäller hörsel, balans, finmotorik, vikt, lipider, glukos, blodtryck samt kongenitala hjärtfel, dvs de kardiovaskulära riskfaktorerna och sinnesfunktioner (16-19). Detta stöder vår hypotes om en förlångsammad cell cykel (Cell Cycle Delay Hypothesis = CCDH) d.v.s. att graden av genetisk avvikelse och inte bara karyotypen spelar roll. Genetiskt sjuka celler har en längre cell cykel än friska celler, vilket leder till att färre celldelningar hinns med under organutvecklingen. Detta kan förklara litenheten av strukturer där cell cykeln under en kort tid under fosterperioden skulle varit kraftigt uppreglerad. T.ex. anomalier av hjärtat och de stora artärerna, micrognati, små nackkotor, infertilitet och hästskonjure. Ett minskat antal muskelceller och bindvävsceller kan minska elasticiteten i aortas kärlvägg, vilket vid TS förklarar aortarotsdilatation, ökad endoteldysfunktion (20), högre puls och blodtryck (21). CCDH kan även ses som en modell för åldrandet: ju färre celler ett organ/struktur har vid födelsen, desto tidigare i livet märks effekterna av senescence och apoptos.


Vi vill söka ny kunskap om TS och:
⋅ Prevalens och incidens, morbiditet och mortalitet samt riskfaktorer avseende cancer, hjärt-kärlsjukdom, thyreoidesjukdom, hörselnedsättning. Utveckling över tid samt jämfört med normalpopulationen.
⋅ Morbiditet, mortalitet och komplikationer under graviditet och vid förlossning, risk för missbildningar hos födda barn och resultat vid äggdonation hos kvinnor med TS jämfört med kvinnor i normalpopulationen.

Frågeställning / Hypoteser

Följande behandlingseffekter:
⋅ Reducerar behandling av hypertoni även inom normalområdet risk för hjärtkärlsjukdom? Vilka typer av preparat skall användas?
⋅ Hur påverkar GH och könssteroider under barnaår och pubertet den vuxna kvinnans hälsa och välbefinnande? Vi studerar hjärtkärlsjukdom,osteoporos, hörsel-, röstutveckling, thyroideafunktion, tandmorfologi och tuggfunktion samt kognitiva och psykosociala aspekter.
⋅ Hur påverkar östrogen i adolescens uterustillväxt och bröstutveckling?

Metod: Urval

Inom TC i Göteborg följs ca 150 kvinnor och nya patienter tillkommer. Nationellt följs 400 patienter, internationellt sett ett av de största samlade patientmaterialen. För jämförande studier finns tillgång till en åldersmatchad kontrollgrupp från projektet WHO MONICA (World Health Organization, MONItoring of trends and determinants in CArdiovascular disease) i Göteborg. Även för psykologiska studier och hörsel finns populationsbaserade kontrollmaterial att tillgå.
Interventionsstudier liksom studier av graviditet samt barnuppföljning sker i europeiska och nordiska samarbeten för att få tillräckligt stort patientmaterial.
Från TC i Göteborg har vi tillskapat ett Turnerregister med genetikdata på ca 700 patienter (det första i världen) vilket ska samköras med de stora folkhälsoregistren på SoS, också dessa unika i världen.
Då kvinnorna vid Turnercentrum SU (n=150) och i det nationella, longitudinella projektet(n=400)v är den bäst kartlagda TS populationen i världen, är i olika åldersgrupper och har varierande behandlingsbakgrund och vi har tillgång till populationsbaserade kontrollgrupper samt folkhälsoregister kan våra studier ge underlag för värdefull kunskap med hög vetenskaplig kvalitet.

Metod: Intervention

Longitudinella studier av morbiditet, mortalitet och given behandling (GH, könssteroider)
Vi har påbörjat 10-årskontroll. Data från anamnes, läkemedelsbehandling, undersökning av endokrinolog, gynekolog, öron-, tandläkare, psykolog, logoped, laboratorieprover samt resultat av DEXA, EKG, ultraljud och MR hjärta, audiometri, röstinspelning, tandröntgen, EMG, funktionsanalys mm registreras (c:a 300 variabler) och samkörs med data från övriga nationella centra, vårt Turnerregister samt folkhälsoregister (ICD diagnoser).
För studier av livskvalitet sker skattning av livskvalitet och välbefinnande med Psychological General Wellbeing (PGWB) och National Health Profile (NHP) och jämförs med behandlingsdata, start- och 5-årsdata.

Interventionsstudie av hjärt-kärlsjukdom:
En multicenterstudie (Århus, London, och Göteborg)med blodtrycksbehandling (betablockad jämfört med angiotensin-II-antagonister) planeras för att skapa riktlinjer för blodtrycksgräns för behandling och vilket/vilka preparat som är optimala för TS kvinnor beroende på grad av kardiovaskulär risk (medfödda hjärtfel bl.a.). Hittills har riktlinjer för behandling av hypertoni i befolkningen betr. gränser och preparat använts. Betablockad har ofta valts som förstahandsbehandling vid Marfans syndrom, som också har en känd ökad incidens av aortadissektion (33). Ansökan avser den svenska delen av projektet. Studien är ointressant för läkemedelsindustrin då preparaten redan är registrerade för hypertoni. Enl powerberäkning är 120 TS kvinnor tillräckligt för endpoints (aortarotsbredd, vänsterkammarfunktion, puls, 24-timmars blodtryck, stresshormoner).
Interventionsstudie östrogeneffekter på och uterusstorlek
I en prospektiv randomiserad dubbel blind multicenterstudie (Hilleröd, Randers, Århus, Göteborg,) inkluderas flickor med TS (15-25 år) som uppnått slutlängd och avslutat pubertetsinduktion. Behandling sker med vanlig dos östradiol (2mg dgl, plus placebo) respektive högdos (4 mg dgl). Totalt 20 pat i varje grupp enligt powerberäkning (alfa 0,05 och beta 0,80).
Utvärdering sker en gång/år i 5 år av uterusstorlek, endometrium och ovarier med Doppler, MR samt hormonanalyser, IGF1, thyreoidea-, lever- och njurfunktion samt lipider.

Metod: Datainsamling

I samarbete med IVF-kliniker i Norden samlas retrospektivt journaldata för kvinnor med TS som genomgått äggdonation och friska kvinnor som genomgått äggdonation resp konventionell IVF-behandling (matchade för ålder och paritet). Morbiditet, mortalitet och förlossningsutfall jämförs. Barndata hämtas från förlossnings och barnhälsovårdsjournaler.
Med 60 gravida TS upptäcks en 4 gånger ökad risk för hypertoni (28% eller mer hypertensiva komplikationer) 80% "power", alfa=0,05.

Metod: Databearbetning

Turnerregistret samkörs med populationsdata från folkhälsoregistren; Medicinska födelse-, Missbildnings-, Dödsorsaks-, Sjukvårdskonsumtions- och Cancerregistret avseende sjukdomsförekomst, mortalitet, graviditetskomplikationer, förlossningsutfall (prematuritet, asfyxi, missbildningar).


Låg risk för cancer, hög risk för för tidig död i hjärtkärlsjukdom har beskrivits vid TS (7, 22), men allmänt saknas välbelagd kunskap om morbiditet och mortalitet pga att kontrollerade studier av stora patientgrupper saknas.
Även systematiserad uppföljning av vuxna kvinnor med TS avseende långtidseffekter av modern behandlingsstrategi med GH och könssteroider saknas. Vi har internationellt unika longitudinella data avseende exakta hormonbehandlingar och fenotyp, liksom gynekologiska, psykosociala, audiologiska, och odontologiska variabler, delvis från födelse upp till vuxen ålder, unika genetikdata (svenskt Turnerregister) samt tillgång till folkhälsoregister.
Få kvinnor med TS har spontan pubertetsutveckling och menarche (10%), ca 3% är fertila, alla riskerar prematur menopaus. Östrogen och androgen ges för pubertetsinduktion och bröstutveckling från barndomen. Trots kunskap om hur dygnsvariation för östradiol ser ut i olika pubertetsperioder, och trots att olika hormonkombinationer givits är få flickor med TS nöjda med sin bröstutveckling. Uterus hos friska flickor växer flera år efter menarche, och avslutad längdtillväxt. Vi fann (opublicerade data) att uterus vid ultraljudsbedömning är avsevärt mindre än hos normala kvinnor (23). Samband mellan uterustillväxt och hormonsubstitution har påvisats (24). Möjligen är given dos/behandlingstid otillräcklig för uterustillväxt. Om den ökade missfallsrisk som påvisats efter spontan graviditet och efter äggdonation är sekundär till könshormonbrist, uterus med låg tillväxtpotential eller endometriedefekter är okänt (25).
Vår begränsade kunskap om risker vid graviditet och hälsan hos födda barn baseras på små studier utan kontrollgrupper (9-11). Ökad risk för graviditetshypertoni, havandeskapsförgiftning, aortadissektion/ruptur med mödramortalitet på 2% samt ökad frekvens missbildningar hos barnen har rapporterats (26-27). Orsakssamband och riskfaktorer är ej kända. Då äggdonation är tillåtet i Sverige sedan 2003 kommer sannolikt antalet graviditeter att öka.
För tidig död i hjärtkärlsjukdom, speciellt aortadissektion även i unga år, har uppmärksammats internationellt (7). Vi fann medfödda hjärtfel och hypertoni i nästan 20% av TS jämfört med 0.1% resp 3% i det åldersmatchade populationsurvalet (17) och aortadissektion i 4-6% mot 0.0001% fr.a. vid ung ålder (28, 29). Fall har beskrivits även under graviditet (26). Vi och en amerikansk kollega samlar alla TS fall av aortadissektion på en hemsida (The International Turner Syndrome Dissection Registry). Aortadilatation och ökad endoteldysfunktion har beskrivits (20), och graden av mosaik (% 45X) är positivt associerad med kardiovaskulära riskfaktorer (19).
Vi har påvisat att nästan varannan TS kvinna drabbas av hypotyreos och tidigt insatt Levaxin rekommenderas för att minimera riskerna för hyperlipidemi (30). Vi fann också att patologiska levervärden har en stark koppling till kolesterol och reverseras vid viktnedgång och sänkning av lipider.
Vad gäller psykosocial hälsa har i avhandling och våra tvärsnittstudier visats att hormonbehandling korrelerade positivt och självrapporterad nedsatt hörsel negativt till psykiskt fungerande, liksom högre ålder (31).
TS förorsakar tillväxtstörningar i ansiktsskelett och anläggningsrubbningar i tänder (32). Motsägande resultat har publicerats avseende GH effekter på ansiktsskelett, studier av tandmineraliseringsgrad saknas. I samarbete med Uppsala har 86 kvinnor undersökts med avseende på avvikelser i ansikts och tandmorfologi.
Behandlingseffekter av östrogen på hörselnedsättning, röstfunktion och kommunikativ förmåga är oklar.


Vi har världens mest omfattande longitudinella kartläggning av genotyp och fenotyp hos flickor och kvinnor med TS. Därtill samarbeten med nationella, nordiska och internationella välrenommerade Turnerexperter samt tillgång till modern molekylärbiologisk metodik. Kunskap om koppling mellan å ena sidan genomets metyleringsgrad och morbiditet å andra sidan (grad och typ) kommer att ge ny kunskap om orsakssamband avseende väsentliga folksjukdomar vid TS. Detta kommer förhoppningsvis att leda till nya, behandlingsvägar såväl farmakologiskt som profylaktiskt, vilka blir mer effektiva ur kostnads- och biverkningssynpunkt även hos normalbefolkningen. För kvinnor med TS bidrar dessa studier till att bättre förebygga, behandla och prognosticera morbiditet, en minskad mortalitet i unga år samt minskade risker för allvarliga komplikationer särskilt hos dem som önskar graviditet. Unik kunskap om TS kvinnans barns hälsa inhämtas.


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6. Barrenäs M-L, Landin-Wilhemsen, K and Hanson C. Ear and hearing in relation to genotype and growth in Turner Syndrome. Hear. Res. 2000;144:21-28.
7. Lin AE, Lippe B, Rosenfeld RG. Further delineation of aortic dilation, dissection and rupture in patients with Turner Syndrome. Pediatrics 1998;102:102-110.
8. Foudila T, Hovatta O, Söderström-A V. Turner’s syndrome and pregnancies after oocyte donation. Human reprod 1999;1282):532-535.
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12. Saenger P, Albertsson-Wikland K, Conway GS, Davenport M, Gravholt CH, Hintz R, Hovatta O, Hultcrantz M, Landin-Wilhelmsen K, Lin A, Lippe B, Pasquino AM, Ranke MB, Rosenfeld R, Silberbach M. Recommendations for the diagnosis and management of Turner Syndrome. J Clin Endocrinol Metab 2001;86:3061-3069.
13. Bondy CA for the Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner syndrome study group. J Clin Endocrinol Metab 2007;92(1):10-25.
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15. Chu CE, Donaldson MDC, Kelnar CJH, Smail PJ, Greene SA, Paterson WF, Connor JM. Possible role of imprinting in the Turner fenotype. J Med Genet 1994; 31:840-842.
16. Skuse DH, James RS, Bishop DVM, et al. Evidence from Turners syndrome of an imprinted X-linked locus affecting cognitive function. Nature 1997; 387: 705-707.
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18. Hanson L, Bryman I, Barrenäs M-L, Janson PO, Wahlström J, Albertsson-Wikland K, Hanson C. Genetic analysis of mosaicism in 53 women with Turner syndrome. Hereditas 2001;134:153-159.
19. El-Mansoury M, Barrenäs M-L, Bryman I, Hanson C, Larsson C, Wilhelmsen L, Landin-Wilhelmsen K. Chromosomal mosaicism mitigates cardiovascular risk factors and stigmata in Turner syndrome. Clin Endocrinol 2007;66:744-751.
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22. Gravholt CH, Landin-Wilhelmsen K, Stochholm K, Hjerrid BE, Ledet T, Djurhuus CB, Sylvén L, Baandrup U, Kristensen BO, Christiansen JS. Aortic dissection in Turner Syndrome. Cardiol Young 2006;16:430-436.
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DNA- och proteinkartläggning samt behandlingseffekter i relation till tidigt åldrande vid Turners syndrom (TS) - mortalitet, morbiditet och fertilitet., from FoU i Sverige