Affordable Access

Access to the full text

Compound Heterozygous and Homozygous Mutations of the TSHβ Gene as a Cause of Congenital Central Hypothyroidism in Europe

Authors
  • Karges, Beate
  • LeHeup, Bruno
  • Schoenle, Eugen
  • Castro-Correia, Cintia
  • Fontoura, Manuel
  • Pfäffle, Roland
  • Andler, Werner
  • Debatin, Klaus-Michael
  • Karges, Wolfram
Type
Published Article
Journal
Hormone Research in Paediatrics
Publisher
S. Karger AG
Publication Date
Sep 10, 2004
Volume
62
Issue
3
Pages
149–155
Identifiers
DOI: 10.1159/000080071
PMID: 15297803
Source
Karger
Keywords
License
Green
External links

Abstract

Background: Thyroid hormones are crucial for normal growth and central nervous system development. In recent years, germline variants of the TSHβ subunit gene have been identified as a cause of congenital TSH deficiency. Methods: We performed a genetic and clinical study in children from four European countries diagnosed with congenital isolated central hypothyroidism. Results: TSHβ gene analysis revealed compound heterozygosity for 145C→T (Q49X) and 313delT (C105Vfs114X) in 1 infant and homozygous mutation 313delT (C105Vfs114X) in 5 patients. Although all presented with typical symptoms of hypothyroidism, diagnosis and treatment was delayed until 3–5 months in 5 of 6 patients. In a longitudinal sibpair analysis, thyroxine substitution initiated immediately after birth was effective to prevent developmental delay and growth retardation. Conclusion: Clinical awareness is required to detect hypothyroidism due to TSHβ mutations, which is not identified by TSH-based newborn screening. TSHβ variants C105Vfs114X and Q49X are the most frequent cause of this severe disorder in Europe, now for the first time observed in compound heterozygous state.

Report this publication

Statistics

Seen <100 times