Startseite Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
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Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion

  • Taise Lima Oliveira Cerqueira , Aurore Carré , Lucie Chevrier , Gabor Szinnai , Elodie Tron , Juliane Léger , Sylvie Cabrol , Chrystelle Queinnec , Nicolas De Roux , Mireille Castanet , Michel Polak und Helton Estrela Ramos ORCID logo EMAIL logo
Veröffentlicht/Copyright: 19. August 2014
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 28 Heft 7-8

Abstract

Context: Thyroid dysgenesis may be associated with loss-of-function mutations in the thyrotropin receptor (TSHR) gene.

Objectives: The aim of this study was to characterize a novel TSHR gene variant found in one patient harboring congenital hypothyroidism (CH) from a cohort of patients with various types of thyroid defects.

Materials and methods: This cross-sectional cohort study involved 118 patients with CH and their family members, including 45 with familial and 73 with sporadic diseases. The thyroid gland was normal in 23 patients, 25 patients had hypoplasia, 25 hemithyroid agenesis, 21 had athyreosis, and 21 had ectopy. Genomic DNA was extracted, and 10 exons of the TSHR gene were amplified and sequenced. Mutations in other candidate genes were investigated. Ortholog alignment was performed, and TSHR functional assays were evaluated.

Results: We identified one previously unknown missense variation in the hinge region (HinR) of the TSHR gene (p.S304R) in one patient with thyroid hypoplasia. This variant is conserved in our ortholog alignment. However, the p.S304R TSHR variant presented a normal glycosylation pattern and signal transduction activity in functional analysis.

Conclusion: We report the ocurrence of a novel nonsynonymous substitution in the HinR of the large N-terminal extracellular domain of the TSHR gene in a patient with thyroid hypoplasia. In contrast with four others in whom TSHR mutations of the hinge portion were previously identified, the p.S304R TSHR variation neither affected TSH binding nor cAMP pathway activation. This TSHR gene variant was documented in a CH patient, but the current data do not support its role in the clinical phenotype.

Keywords: congenital hypothyroidism; hinge portion; thyroid dysgenesis; TSH receptor; variants
Corresponding author: Helton Estrela Ramos, Federal University of Bahia, Health and Science Institute, Department of Biorregulation, Avenida Reitor Miguel Calmon, S/N, Sala 301, Vale do Canela, 40110-102 Salvador, Bahia, Brazil, Phone: +55 71 3283 8890, Fax: +55 71 3283 8927, E-mail: , http://orcid.org/0000-0002-2900-2099; Curso de Pós-Graduação em Biotecnologia em Saúde e Medicina Investigativa, Centro de Pesquisa Gonçalo Moniz-FIOCRUZ/BA, Salvador, Bahia, Brazil; INSERM U845, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Pediatric Endocrine Unit, Centre des Maladies Endocriniennes Rares de la Croissance, Hôpital Necker Enfants Malades, AP-HP, Paris, France; and Departamento de Biorregulação, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Bahia, Brazil

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Received: 2014-5-13
Accepted: 2014-7-14
Published Online: 2014-8-19
Published in Print: 2015-7-1

©2015 by De Gruyter

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Thyroid
  3. Thyroid disorders revisited
  4. Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
  5. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
  6. Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients
  7. Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism
  8. Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
  9. Neonatal thyroid storm accompanied with severe anaemia
  10. Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
  11. Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia
  12. Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study
  13. Papillary thyroid cancer and autoimmune polyglandular syndrome
  14. Review article
  15. Should radioiodine be the first-line treatment for paediatric Graves’ disease?
  16. Image in pediatric endrocrinology
  17. Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease
  18. Original articles
  19. Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism
  20. Rickets and vitamin D deficiency in Alaska native children
  21. Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants
  22. Parents’ experiences of having a baby with ambiguous genitalia
  23. Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty
  24. Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
  25. Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
  26. Influence of the body weight on the onset and progression of puberty in boys
  27. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
  28. Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
  29. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
  30. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods
  31. Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
  32. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
  33. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
  34. Patient reports
  35. 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
  36. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
  37. Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
  38. Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
  39. Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
  40. Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
  41. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
  42. Donohue syndrome: a new case with a new complication
  43. Euprolactinemic galactorrhea secondary to domperidone treatment
  44. 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
  45. Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
  46. Short communication
  47. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1
https://doi.org/10.1515/jpem-2014-0194
Schlagwörter für diesen Artikel
congenital hypothyroidism; hinge portion; thyroid dysgenesis; TSH receptor; variants

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Thyroid
  3. Thyroid disorders revisited
  4. Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
  5. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
  6. Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients
  7. Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism
  8. Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
  9. Neonatal thyroid storm accompanied with severe anaemia
  10. Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
  11. Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia
  12. Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study
  13. Papillary thyroid cancer and autoimmune polyglandular syndrome
  14. Review article
  15. Should radioiodine be the first-line treatment for paediatric Graves’ disease?
  16. Image in pediatric endrocrinology
  17. Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease
  18. Original articles
  19. Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism
  20. Rickets and vitamin D deficiency in Alaska native children
  21. Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants
  22. Parents’ experiences of having a baby with ambiguous genitalia
  23. Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty
  24. Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
  25. Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
  26. Influence of the body weight on the onset and progression of puberty in boys
  27. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
  28. Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
  29. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
  30. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods
  31. Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
  32. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
  33. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
  34. Patient reports
  35. 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
  36. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
  37. Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
  38. Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
  39. Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
  40. Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
  41. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
  42. Donohue syndrome: a new case with a new complication
  43. Euprolactinemic galactorrhea secondary to domperidone treatment
  44. 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
  45. Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
  46. Short communication
  47. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1
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