Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.

ABSTRACT:

Background

A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined.

Methods

We sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity, including 90 probands from consanguineous families, and investigated the extent to which mutations cosegregated with obesity and affected receptor function. We evaluated metabolic, endocrine, and immune function in probands and affected relatives.

Results

Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations--7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subje

SUBMITTER: Farooqi IS 

PROVIDER: S-EPMC2670197 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature