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

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.

Citation

Aryel Furman, Zeina Hannoush, Francisco Barrera Echegoyen, Alexandra Dumitrescu, Samuel Refetoff, Roy E Weiss. Novel DIO1 Gene Mutation Acting as Phenotype Modifier for Novel Compound Heterozygous TPO Gene Mutations Causing Congenital Hypothyroidism. Thyroid : official journal of the American Thyroid Association. 2021 Oct;31(10):1589-1591

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PMID: 34128397

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