Article detail · 2016
Comprehensive Screening of Eight Known Causative Genes in Congenital Hypothyroidism With Gland in Situ
Journal
The Journal of Clinical Endocrinology & MetabolismISSN 0021-972X
The ISSN points to another catalog journal; the name is from the YÖKSİS record.
- Year
- 2016
- Type
- article
Data source split
- YÖKSİS YÖKSİS article record
- YÖKSİS venue The Journal of Clinical Endocrinology & Metabolism
- Catalog match (ISSN) Journal of Clinical Endocrinology and Metabolism
- OpenAlex OpenAlex enrichment (abstract, citations, topics)
Abstract
OpenAlex · English
CONTEXT: Lower TSH screening cutoffs have doubled the ascertainment of congenital hypothyroidism (CH), particularly cases with a eutopically located gland-in-situ (GIS). Although mutations in known dyshormonogenesis genes or TSHR underlie some cases of CH with GIS, systematic screening of these eight genes has not previously been undertaken. OBJECTIVE: Our objective was to evaluate the contribution and molecular spectrum of mutations in eight known causative genes (TG, TPO, DUOX2, DUOXA2, SLC5A5, SLC26A4, IYD, and TSHR) in CH cases with GIS. Patients, Design, and Setting: We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico. PATIENTS, DESIGN, AND SETTING: We screened 49 CH cases with GIS from 34 ethnically diverse families, using next-generation sequencing. Pathogenicity of novel mutations was assessed in silico. RESULTS: Twenty-nine cases harbored likely disease-causing mutations. Monogenic defects (19 cases) most commonly involved TG (12), TPO (four), DUOX2 (two), and TSHR (one). Ten cases harbored triallelic (digenic) mutations: TG and TPO (one); SLC26A4 and TPO (three), and DUOX2 and TG (six cases). Novel variants overall included 15 TG, six TPO, and three DUOX2 mutations. Genetic basis was not ascertained in 20 patients, including 14 familial cases. CONCLUSIONS: The etiology of CH with GIS remains elusive, with only 59% attributable to mutations in TSHR or known dyshormonogenesis-associated genes in a cohort enriched for familial cases. Biallelic TG or TPO mutations most commonly underlie severe CH. Triallelic defects are frequent, mandating future segregation studies in larger kindreds to assess their contribution to variable phenotype. A high proportion (∼41%) of unsolved or ambiguous cases suggests novel genetic etiologies that remain to be elucidated.
Topics
Citations
OpenAlex cited_by_count. Not a WoS or Scopus citation count; those sources have no separate column here.
116 citations
OpenAlex cited_by_count (cache / database)
8 publications in the local catalog that cite this work (OpenAlex reference match; not the full global list).
- Digenic DUOX1 and DUOX2 Mutations in Cases With Congenital Hypothyroidism 2017
- Genetic testing can change diagnosis and treatment in children with congenital hypothyroidism 2023
- Genetic testing can change diagnosis and treatment in children with congenital hypothyroidism 2023
- Genetic testing can change diagnosis and treatment in children with congenital hypothyroidism. 2023
- Genetic testing can change diagnosis and treatment in children with congenital hypothyroidism 2023
- Screening of 23 candidate genes by next-generation sequencing of patients with permanent congenital hypothyroidism: novel variants in TG, TSHR, DUOX2, FOXE1, and SLC26A7 2021
- Genetic Analyses in a Cohort of Pediatric Patients with Congenital Hypothyroidism Based on Congenital Hypothyroidism Consensus Guideline 2024
- Thyroglobulin (TG) gene variants in cases with congenital goiter 2025