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

Aryel Furman, Zeina Hannoush, Francisco Barrera Echegoyen, Alexandra Dumitrescu, Samuel Refetoff, Roy E. Weiss

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1589-1591
Number of pages3
JournalThyroid
Volume31
Issue number10
DOIs
StatePublished - Oct 1 2021
Externally publishedYes

Keywords

  • congenital hypothyroidism
  • deiodinase
  • reverse T3
  • thyroperoxidase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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