Artikel
Lizenziert
Nicht lizenziert
Erfordert eine Authentifizierung
TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis
-
Hakan Cangul
,
Zehra Aycan
Veröffentlicht/Copyright:
24. Mai 2012
Abstract
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multicase families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.
Keywords: autosomal recessive; congenital hypothyroidism; consanguineous; mutation; thyroid dysgenesis; TSHR
Received: 2012-2-21
Accepted: 2012-4-11
Published Online: 2012-05-24
Published in Print: 2012-06-01
©2012 by Walter de Gruyter Berlin Boston
Sie haben derzeit keinen Zugang zu diesem Inhalt.
Sie haben derzeit keinen Zugang zu diesem Inhalt.
Artikel in diesem Heft
- Masthead
- Masthead
- Reviews
- Growth failure in children with cystic fibrosis
- Approach to the management of slipped capital femoral epiphysis and primary hyperparathyroidism
- Original Articles
- Thyroid developmental anomalies among first-degree relatives of children with thyroid dysgenesis and congenital hypothyroidism
- TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis
- When to operate on ovarian cysts in children?
- Partial anomalous pulmonary venous return is common in Turner syndrome
- Uterine development in patients with Turner syndrome: Relation to hormone replacement therapy and karyotype
- Ovarian and uterine ultrasonography and relation to puberty in healthy girls between 6 and 16 years in the Turkish population: a cross-sectional study
- Assessment of gonadal function in boys and adolescents at the diagnosis of neoplastic disease
- Environmental and genetic factors influence age at menarche in women with polycystic ovary syndrome
- Vitamin D status in children with Hashimoto thyroiditis
- Non-invasive measurement of adrenal response after standardized exercise tests in prepubertal children
- Bone metabolism biomarkers, body weight, and bone age in healthy Brazilian male adolescents
- Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta
- Evaluation and comparison of safety, convenience and cost of administering intravenous pamidronate infusions to children in the home and ambulatory care settings
- Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey
- Audiologic evaluation in pediatric patients with type 1 diabetes mellitus
- An after-school dance and lifestyle education program reduces risk factors for heart disease and diabetes in elementary school children
- Evaluation of neutrophil gelatinase-associated lipocalin in normoalbuminuric normotensive type 1 diabetic adolescents
- The association of serum lipocalin-2 levels with metabolic and clinical parameters in obese children: a pilot study
- Metabolic disorders in vertically HIV-infected children: future adults at risk for cardiovascular disease
- Ghrelin and growth hormone secretagogue receptor (GHSR) genes are not commonly involved in growth or weight abnormalities in an Israeli pediatric population
- Patient Reports
- Splenogonadal fusion and sex reversal
- The earlier described mutation (c.307C>T [p.R103X]) in the SRD5A2 gene causing a 46,XY female phenotype
- Sertoli cell tumor and intratubular germ cell neoplasia located in separate gonads in an adolescent patient with complete androgen insensitivity: a case report and review of literature
- Seizure due to somatostatin analog discontinuation in a case diagnosed as congenital hyperinsulinism novel mutation
- Simultaneous onset and similar course of type 1 diabetes mellitus in monozygotic twins (a 4-year follow-up)
- 17β-Hydroxysteroid dehydrogenase type 3 deficiency as a result of a homozygous 7 base pair deletion in 17βHSD3 gene
- Clinical and image-guided chorioretinal findings in long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
- Influence of HLA DQ 2/8 genotypes in predisposing type 1 diabetes in siblings of a Saudi family with paternally inherited chromosomal translocations
- An unusual association between growth hormone deficiency and a middle cranial fossa arachnoid cyst
- Type 2 diabetes mellitus in a young girl: ominous presentation and atypical course
- Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature
- A case of Rabson-Mendenhall syndrome with a novel mutation in the tyrosine kinase domain of the insulin receptor gene complicated by medullary sponge kidney
- Persistent hyperinsulinemic hypoglycemia of infancy
- Septo-optic dysplasia and hemophagocytic lymphohistiocytosis in an infant
- Primary familial hypomagnesemia syndrome: a new approach in treatment
- A case of congenital hypothyroidism in PHACE syndrome
- Short Communication
- Is vitamin D deficiency a feature of pediatric celiac disease?
- Letters to the Editor
- Authors’ reply to “The appropriate use of sensitive tests of hypothalamic-pituitary-adrenal axis suppression”
- Diagnosis of non-alcoholic fatty liver disease in obese children
- Meetings
- Meetings Calendar
Schlagwörter für diesen Artikel
autosomal recessive;
congenital hypothyroidism;
consanguineous;
mutation;
thyroid dysgenesis;
TSHR
Artikel in diesem Heft
- Masthead
- Masthead
- Reviews
- Growth failure in children with cystic fibrosis
- Approach to the management of slipped capital femoral epiphysis and primary hyperparathyroidism
- Original Articles
- Thyroid developmental anomalies among first-degree relatives of children with thyroid dysgenesis and congenital hypothyroidism
- TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis
- When to operate on ovarian cysts in children?
- Partial anomalous pulmonary venous return is common in Turner syndrome
- Uterine development in patients with Turner syndrome: Relation to hormone replacement therapy and karyotype
- Ovarian and uterine ultrasonography and relation to puberty in healthy girls between 6 and 16 years in the Turkish population: a cross-sectional study
- Assessment of gonadal function in boys and adolescents at the diagnosis of neoplastic disease
- Environmental and genetic factors influence age at menarche in women with polycystic ovary syndrome
- Vitamin D status in children with Hashimoto thyroiditis
- Non-invasive measurement of adrenal response after standardized exercise tests in prepubertal children
- Bone metabolism biomarkers, body weight, and bone age in healthy Brazilian male adolescents
- Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta
- Evaluation and comparison of safety, convenience and cost of administering intravenous pamidronate infusions to children in the home and ambulatory care settings
- Clinical profile and etiologies of children with central diabetes insipidus: a single-center experience from Turkey
- Audiologic evaluation in pediatric patients with type 1 diabetes mellitus
- An after-school dance and lifestyle education program reduces risk factors for heart disease and diabetes in elementary school children
- Evaluation of neutrophil gelatinase-associated lipocalin in normoalbuminuric normotensive type 1 diabetic adolescents
- The association of serum lipocalin-2 levels with metabolic and clinical parameters in obese children: a pilot study
- Metabolic disorders in vertically HIV-infected children: future adults at risk for cardiovascular disease
- Ghrelin and growth hormone secretagogue receptor (GHSR) genes are not commonly involved in growth or weight abnormalities in an Israeli pediatric population
- Patient Reports
- Splenogonadal fusion and sex reversal
- The earlier described mutation (c.307C>T [p.R103X]) in the SRD5A2 gene causing a 46,XY female phenotype
- Sertoli cell tumor and intratubular germ cell neoplasia located in separate gonads in an adolescent patient with complete androgen insensitivity: a case report and review of literature
- Seizure due to somatostatin analog discontinuation in a case diagnosed as congenital hyperinsulinism novel mutation
- Simultaneous onset and similar course of type 1 diabetes mellitus in monozygotic twins (a 4-year follow-up)
- 17β-Hydroxysteroid dehydrogenase type 3 deficiency as a result of a homozygous 7 base pair deletion in 17βHSD3 gene
- Clinical and image-guided chorioretinal findings in long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency
- Influence of HLA DQ 2/8 genotypes in predisposing type 1 diabetes in siblings of a Saudi family with paternally inherited chromosomal translocations
- An unusual association between growth hormone deficiency and a middle cranial fossa arachnoid cyst
- Type 2 diabetes mellitus in a young girl: ominous presentation and atypical course
- Marked increase of final height by long-term aromatase inhibition in a boy with idiopathic short stature
- A case of Rabson-Mendenhall syndrome with a novel mutation in the tyrosine kinase domain of the insulin receptor gene complicated by medullary sponge kidney
- Persistent hyperinsulinemic hypoglycemia of infancy
- Septo-optic dysplasia and hemophagocytic lymphohistiocytosis in an infant
- Primary familial hypomagnesemia syndrome: a new approach in treatment
- A case of congenital hypothyroidism in PHACE syndrome
- Short Communication
- Is vitamin D deficiency a feature of pediatric celiac disease?
- Letters to the Editor
- Authors’ reply to “The appropriate use of sensitive tests of hypothalamic-pituitary-adrenal axis suppression”
- Diagnosis of non-alcoholic fatty liver disease in obese children
- Meetings
- Meetings Calendar
