[An analysis of GNAS and THRA gene mutations in children with congenital hypothyroidism]

Area of Science:

• Genetics
• Endocrinology
• Pediatrics

Background:

• Congenital hypothyroidism (CH) is a condition requiring early diagnosis and treatment.
• Genetic factors play a role in the etiology of CH.
• The involvement of specific genes like GNAS and THRA in CH requires further elucidation.

Purpose of the Study:

• To investigate the association between mutations in the stimulatory G protein α subunit (GNAS) and thyroid hormone receptor α (THRA) genes and clinical phenotypes in children with CH.
• To identify potential genetic markers for CH.

Main Methods:

• Next-generation sequencing was used to screen for mutations in the GNAS and THRA genes in 70 children diagnosed with CH.
• Bioinformatics software and ACMG/AMP guidelines were employed to analyze the pathogenicity of identified gene variants.
• Clinical phenotypes of affected children were correlated with genetic findings.

Main Results:

• Nine missense mutations in the GNAS gene (including six novel mutations) were found in three patients (4.3%).
• Two GNAS gene mutations, c.301C>T(p.R101C) and c.334G>A(p.E112K), were predicted to be pathogenic.
• One THRA gene polymorphism (c.508A>G(p.I170V)) was detected in four patients, but THRA mutations were not found to be significantly associated with CH.
• Children with GNAS mutations exhibited varying degrees of hypothyroidism.

Conclusions:

• GNAS gene mutations are implicated in the development of CH and are associated with diverse clinical presentations.
• THRA gene mutations do not appear to be a significant factor in the pathogenesis of CH.
• Further research is warranted to fully understand the genetic landscape of CH.