Functional Domain Mapping of TPO: Insights From 6 Variants in Sudanese Kindreds With Congenital Hypothyroidism.

ABSTRACT:

Context

Congenital hypothyroidism (CH) is a leading cause of preventable intellectual disability worldwide if left untreated. Thyroid peroxidase (TPO) is a key enzyme that uses hydrogen peroxide from the DUOX/DUOXA system to oxidize iodide for thyroid hormone synthesis.

Objective

This work aimed to identify the pathogenic TPO variants responsible for CH.

Methods

Variants identified by whole-exome sequencing were analyzed using in silico tools and structural modeling for pathogenicity. TPO function was assessed through in vitro studies on intracellular trafficking, enzymatic activity, and interaction with DUOX/DUOXA proteins.

Results

Six TPO variants were identified: p.G395D, p.V618M, p.M706V, and p.T725P in family 1, and p.R648G and p.G771R in families 2 and 3,

SUBMITTER: Islam MS 

PROVIDER: S-EPMC12684696 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature