Hussain, M.S., Baig, S.M., Neumann, S., Nürnberg, G., Farooq, M., Ahmad, I.A., Alef, T., Hennies, Hans C., Technau, M., Altmüller, J., Frommolt, P., Thiele, H., Noegel, A.A. and Nürnberg, P. (2012) A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function. The American Journal of Human Genetics, 90 (5). pp. 871-878. ISSN 0002-9297Metadata only available from this repository.
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 mutation's identification as the causal variant. Fibroblasts obtained from one of the patients showed multiple and fragmented centrosomes, disorganized microtubules, and reduced growth rate. Similar effects were reported after knockdown of CEP135 through RNA interference; we could provoke them also by ectopic overexpression of the mutant protein. Our findings suggest an additional locus for MCPH at HSA 4q12 (MCPH8), further strengthen the role of centrosomes in the development of MCPH, and place CEP135 among the essential components of this important organelle in particular for a normal neurogenesis.
|Additional Information:||Unmapped bibliographic data: ST - A truncating mutation of CEP135 causes primary microcephaly and disturbed centrosomal function [Field not mapped to EPrints] C2 - PMC3376485 [Field not mapped to EPrints] AD - Cologne Center for Genomics, University of Cologne, Cologne, Germany. [Field not mapped to EPrints] AN - 22521416 [Field not mapped to EPrints]|
|Uncontrolled Keywords:||Carrier Proteins/*genetics/metabolism|
|Subjects:||Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
|Depositing User:||Hans Hennies|
|Date Deposited:||11 Jul 2016 14:58|
|Last Modified:||29 Jul 2016 13:09|
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