A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function.

ABSTRACT: Autosomal-recessive primary microcephaly (MCPH) is a rare congenital disorder characterized by intellectual disability, reduced brain and head size, but usually without defects in cerebral cortical architecture, and other syndromic abnormalities. MCPH is heterogeneous. The underlying genes of the seven known loci code for centrosomal proteins. We studied a family from northern Pakistan with two microcephalic children using homozygosity mapping and found suggestive linkage for regions on chromosomes 2, 4, and 9. We sequenced two positional candidate genes and identified a homozygous frameshift mutation in the gene encoding the 135 kDa centrosomal protein (CEP135), located in the linkage interval on chromosome 4, in both affected children. Post hoc whole-exome sequencing corroborated this mu

SUBMITTER: Hussain MS 

PROVIDER: S-EPMC3376485 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature