A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome.

ABSTRACT:

Objective

Loss-of-function mutations in IGSF1 result in X-linked central congenital hypothyroidism (CeCH), occurring in isolation or associated with additional pituitary hormone deficits. Intrafamilial penetrance is highly variable and a minority of heterozygous females are also affected. We identified and characterized a novel IGSF1 mutation and investigated its associated phenotypes in a large Irish kindred.

Design, patients and measurements

A novel hemizygous IGSF1 mutation was identified by direct sequencing in two brothers with CeCH, and its functional consequences were characterized in vitro. Genotype-phenotype correlations were investigated in the wider kindred.

Results

The mutant IGSF1 protein (c.2318T > C, p.L773P) exhibited decreased plasma membrane expressi

SUBMITTER: Roche EF 

PROVIDER: S-EPMC6282842 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature