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

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Bond, Jacquelyn; Scott, Sheila; Hampshire, Daniel J; Springell, Kelly; Corry, Peter; Abramowicz, Marc J; Mochida, Ganesh H; Hennekam, Raoul C M; Maher, Eamonn R; Fryns, Jean-Pierre; Alswaid, Abdulrahman; Jafri, Hussain; Rashid, Yasmin; Mubaidin, Ammar; Walsh, Christopher A; Roberts, Emma; Woods, C Geoffrey
Year of Publication: 2003
Journal: Am J Hum Genet
Volume: 73
Issue: 5
Pagination: 1170-7
Date Published: 2003 Nov
Publication Language: eng
ISSN: 0002-9297
Keywords: Amino Acid Sequence, Base Sequence, Brain, Chromosomes, Human, Pair 1, Codon, Nonsense, Consanguinity, DNA Mutational Analysis, Exons, Frameshift Mutation, Genes, Recessive, Haplotypes, Humans, Intellectual Disability, Introns, Male, Microcephaly, Microsatellite Repeats, Mutation, Nerve Tissue Proteins, Pakistan, Phenotype, Polymorphism, Genetic, RNA, Messenger

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.

DOI: 10.1086/379085
Alternate Journal: Am. J. Hum. Genet.