Variable clinical phenotypes in a family with homozygous c.1159G>A mutation in the thyroid peroxidase gene

Horm Res Paediatr. 2014;81(5):356-60. doi: 10.1159/000359922. Epub 2014 Apr 4.

Abstract

Background: Defects in the thyroid peroxidase (TPO) gene have been associated with goitrous congenital hypothyroidism (CH).

Case report: In this study, we report 3 siblings possessing a homozygous mutation, c.1159G>A, but exhibiting different clinical phenotypes in a Malaysian-Malay family. The index patient was diagnosed with CH during a routine neonatal screening but the other 2 siblings appeared to be asymptomatic until the ages of 19 and 12.5, respectively, when they started to develop goiter.

Results and conclusion: The mutation was predicted to interrupt the correct splicing of pre-mRNA and also lead to structural alterations in the functional sites of the mutant TPO. The current results suggest the association of goiter development with a homozygous c.1159G>A mutation, but the CH in the index patient could be triggered by other genetic and epigenetic factors distinct from the c.1159G>A mutation.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Congenital Hypothyroidism* / enzymology
  • Congenital Hypothyroidism* / genetics
  • Congenital Hypothyroidism* / pathology
  • Family
  • Female
  • Goiter* / enzymology
  • Goiter* / genetics
  • Goiter* / pathology
  • Homozygote*
  • Humans
  • Iodide Peroxidase* / genetics
  • Iodide Peroxidase* / metabolism
  • Male
  • Point Mutation*
  • RNA Splicing / genetics

Substances

  • Iodide Peroxidase