Open AccessGLS loss of function causes autosomal recessive spastic ataxia and optic atrophy
Author(s) -
Lynch David S.,
Chelban Viorica,
Vandrovcova Jana,
Pittman Alan,
Wood Nicholas W.,
Houlden Henry
Publication year - 2018
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.522
Subject(s) - medicine , ataxia , loss function , atrophy , disease gene identification , gene duplication , glutamine , genetics , exome sequencing , gene , mutation , biology , phenotype , pathology , amino acid , psychiatry
We describe a consanguineous family in which two brothers were affected by childhood onset spastic ataxia with optic atrophy and loss of motor and language skills. Through a combination of homozygosity mapping and whole‐genome sequencing, we identified a homozygous copy number variant in GLS as the cause. The duplication leads to complete knockout of GLS expression. GLS encodes the brain‐ and kidney‐specific enzyme glutaminase, which hydrolyzes glutamine for the production of glutamate, the most abundant central nervous system neurotransmitter. This is the first report implicating GLS loss of function in human disease.