Mutations in IRS4 are associated with central hypothyroidism.

ABSTRACT:

Background

Four genetic causes of isolated congenital central hypothyroidism (CeH) have been identified, but many cases remain unexplained. We hypothesised the existence of other genetic causes of CeH with a Mendelian inheritance pattern.

Methods

We performed exome sequencing in two families with unexplained isolated CeH and subsequently Sanger sequenced unrelated idiopathic CeH cases. We performed clinical and biochemical characterisation of the probands and carriers identified by family screening. We investigated IRS4 mRNA expression in human hypothalamus and pituitary tissue, and measured serum thyroid hormones and Trh and Tshb mRNA expression in hypothalamus and pituitary tissue of Irs4 knockout mice.

Results

We found mutations in the insulin

SUBMITTER: Heinen CA 

PROVIDER: S-EPMC6161650 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature