A mutation in the serine protease TMPRSS4 in a novel pediatric neurodegenerative disorder.

ABSTRACT:

Background

To elucidate the genetic basis of a novel neurodegenerative disorder in an Old Order Amish pedigree by combining homozygosity mapping with exome sequencing.

Methods and results

We identified four individuals with an autosomal recessive condition affecting the central nervous system (CNS). Neuroimaging studies identified progressive global CNS tissue loss presenting early in life, associated with microcephaly, seizures, and psychomotor retardation; based on this, we named the condition Autosomal Recessive Cerebral Atrophy (ARCA). Using two unbiased genetic approaches, homozygosity mapping and exome sequencing, we narrowed the candidate region to chromosome 11q and identified the c.995C > T (p.Thr332Met) mutation in the TMPRSS4 gene. Sanger sequencing of additional

SUBMITTER: Lahiry P 

PROVIDER: S-EPMC3765793 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature