title: Novel protein-truncating mutations in the ASPM gene in families with autosomal recessive primary microcephaly.
abstract: Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that causes reduction in brain size. Individuals affected with the disorder show a small but architecturally normal cerebral cortex and are associated with mental retardation of mild-to severe form. MCPH is genetically heterogeneous with six loci, and four genes have been identified so far. Homozygous mutations in the ASPM gene, located at MCPH5 locus on chromosome 1q31, are the most common cause of MCPH particularly in the Pakistani population. In the present study, we have ascertained ten Pakistani and one Kashmiri family with primary microcephaly. We screened for potential mutations of the ASPM gene in seven consanguineous families (six Pakistani and one Kashmiri) linked to MCPH5 locus. Two previously reported (8508delGA, W1326X) and four novel sequence variants (Y1712X, I1717X, Y3353X, R3244X) were detected and all were predicted to be protein truncating. The degree of mental retardation in the affected individuals of the seven families varied from mild to moderate, and was not dependent on the location of mutations in the ASPM gene.
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.
authors.forename: Asma
authors.initials: A
authors.lastname: Gul
authors.forename: Muhammad
authors.initials: M
authors.lastname: Tariq
authors.forename: Muhammad Nasim
authors.initials: MN
authors.lastname: Khan
authors.forename: Muhammad Jawad
authors.initials: MJ
authors.lastname: Hassan
authors.forename: Ghazanfar
authors.initials: G
authors.lastname: Ali
authors.forename: Wasim
authors.initials: W
authors.lastname: Ahmad
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D008297:Male; D008831:Microcephaly / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010154:Pakistan
chemical_list: C467202:ASPM protein, human; D009419:Nerve Tissue Proteins