Deficiency of asparagine synthetase causes congenital microcephaly and a progressive form of encephalopathy.

ABSTRACT: We analyzed four families that presented with a similar condition characterized by congenital microcephaly, intellectual disability, progressive cerebral atrophy, and intractable seizures. We show that recessive mutations in the ASNS gene are responsible for this syndrome. Two of the identified missense mutations dramatically reduce ASNS protein abundance, suggesting that the mutations cause loss of function. Hypomorphic Asns mutant mice have structural brain abnormalities, including enlarged ventricles and reduced cortical thickness, and show deficits in learning and memory mimicking aspects of the patient phenotype. ASNS encodes asparagine synthetase, which catalyzes the synthesis of asparagine from glutamine and aspartate. The neurological impairment resulting from ASNS deficiency may b

SUBMITTER: Ruzzo EK 

PROVIDER: S-EPMC3820368 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature