Loss-of-function mutations in PNPLA6 encoding neuropathy target esterase underlie pubertal failure and neurological deficits in Gordon Holmes syndrome.

ABSTRACT:

Context

Gordon Holmes syndrome (GHS) is characterized by cerebellar ataxia/atrophy and normosmic hypogonadotropic hypogonadism (nHH). The underlying pathophysiology of this combined neurodegeneration and nHH remains unknown.

Objective

We aimed to provide insight into the disease mechanism in GHS.

Methods

We studied a cohort of 6 multiplex families with GHS through autozygosity mapping and whole-exome sequencing.

Results

We identified 6 patients from 3 independent families carrying loss-of-function mutations in PNPLA6, which encodes neuropathy target esterase (NTE), a lysophospholipase that maintains intracellular phospholipid homeostasis by converting lysophosphatidylcholine to glycerophosphocholine. Wild-type PNPLA6, but not PNPLA6 bearing these mutations, res

SUBMITTER: Topaloglu AK 

PROVIDER: S-EPMC5393493 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature