Founder effect in the Horn of Africa for an insulin receptor mutation that may impair receptor recycling.

ABSTRACT:

Aims/hypothesis

Genetic insulin receptoropathies are a rare cause of severe insulin resistance. We identified the Ile119Met missense mutation in the insulin receptor INSR gene, previously reported in a Yemeni kindred, in four unrelated patients with Somali ancestry. We aimed to investigate a possible genetic founder effect, and to study the mechanism of loss of function of the mutant receptor.

Methods

Biochemical profiling and DNA haplotype analysis of affected patients were performed. Insulin receptor expression in lymphoblastoid cells from a homozygous p.Ile119Met INSR patient, and in cells heterologously expressing the mutant receptor, was examined. Insulin binding, insulin-stimulated receptor autophosphorylation, and cooperativity and pH dependency of insulin dissociatio

SUBMITTER: Raffan E 

PROVIDER: S-EPMC3071941 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature