Novel DIO1 Gene Mutation Acting as Phenotype Modifier for Novel Compound Heterozygous TPO Gene Mutations Causing Congenital Hypothyroidism

Thyroid. 2021 Oct;31(10):1589-1591. doi: 10.1089/thy.2021.0210. Epub 2021 Jul 16.

Abstract

A family with congenital hypothyroidism was identified with two novel deleterious compound heterozygous thyroid peroxidase (TPO) mutations (c.962C>A, and c.1577C>T). Serum thyroid tests showed higher-than-expected serum-free thyroxine (T4) relative to TT3, while reverse triiodothyronine (rT3) was also elevated. Two siblings manifested a more severe phenotype of developmental delay compared with another sibling and were found to harbor an additional novel heterozygous deleterious iodothyronine deiodinase 1 (DIO1) mutation (c.395G>A). In the context of L-T4 replacement, the decreased D1 activity results in abnormal thyroid hormone metabolism with decreased triiodothyronine (T3) generation from L-T4 and may result in decreased T3 bioavailability during critical stages of development.

Keywords: congenital hypothyroidism; deiodinase; reverse T3; thyroperoxidase.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantigens / genetics*
  • Biomarkers
  • Congenital Hypothyroidism / diagnosis
  • Congenital Hypothyroidism / genetics*
  • DNA-Binding Proteins / genetics*
  • Female
  • Heterozygote*
  • Humans
  • Iodide Peroxidase / genetics*
  • Iron-Binding Proteins / genetics*
  • Male
  • Mutation*
  • Phenotype*
  • Thyroid Function Tests
  • Thyroxine / blood
  • Triiodothyronine / blood

Substances

  • Autoantigens
  • Biomarkers
  • DIDO1 protein, human
  • DNA-Binding Proteins
  • Iron-Binding Proteins
  • Triiodothyronine
  • TPO protein, human
  • Iodide Peroxidase
  • Thyroxine