Variations in PROKR2, but not PROK2, are associated with hypopituitarism and septo-optic dysplasia.

ABSTRACT:

Context

Loss-of-function mutations in PROK2 and PROKR2 have been implicated in Kallmann syndrome (KS), characterized by hypogonadotropic hypogonadism and anosmia. Recent data suggest overlapping phenotypes/genotypes between KS and congenital hypopituitarism (CH), including septo-optic dysplasia (SOD).

Objective

We screened a cohort of patients with complex forms of CH (n = 422) for mutations in PROK2 and PROKR2.

Results

We detected 5 PROKR2 variants in 11 patients with SOD/CH: novel p.G371R and previously reported p.A51T, p.R85L, p.L173R, and p.R268C-the latter 3 being known functionally deleterious variants. Surprisingly, 1 patient with SOD was heterozygous for the p.L173R variant, whereas his phenotypically unaffected mother was homozygous for the variant. We sought

SUBMITTER: McCabe MJ 

PROVIDER: S-EPMC3612801 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature