Protein-truncating mutations in ASPM cause variable reduction in brain size

J Bond, S Scott, DJ Hampshire, K Springell, P Corry, MJ Abramowicz, GH Mochida, RC Hennekam, Eamonn Maher, JP Fryns, A Alswaid, H Jafri, Y Rashid, A Mubaidin, CA Walsh, E Roberts, CG Woods

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    127 Citations (Scopus)


    Mutations in the ASPM gene at the MCPH5 locus are expected to be the most common cause of human autosomal recessive primary microcephaly (MCPH), a condition in which there is a failure of normal fetal brain development, resulting in congenital microcephaly and mental retardation. We have performed the first comprehensive mutation screen of the 10.4-kb ASPM gene, identifying all 19 mutations in a cohort of 23 consanguineous families. Mutations occurred throughout the ASPM gene and were all predicted to be protein truncating. Phenotypic variation in the 51 affected individuals occurred in the degree of microcephaly (5-11 SDs below normal) and of mental retardation (mild to severe) but appeared independent of mutation position.
    Original languageEnglish
    Pages (from-to)1170-1177
    Number of pages8
    JournalAmerican Journal of Human Genetics
    Issue number5
    Publication statusPublished - 1 Nov 2003


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