title: Compound heterozygous ASPM mutations associated with microcephaly and simplified cortical gyration in a consanguineous Algerian family.
abstract: Homozygous mutations in the ASPM gene are a major cause of autosomal recessive primary microcephaly (MCPH). Here we report on a consanguineous Algerian family in which three out of five children presented with severe microcephaly, simplified cortical gyration, mild to severe mental retardation and low to low-normal birth weight. Given the parental consanguinity with the unaffected parents being third cousins once removed, the most probable pattern of inheritance was autosomal recessive. Linkage and mutational analyses identified compound heterozygous truncating mutations within the ASPM gene segregating with MCPH (c.2389C>T [p.Arg797X] and c.7781_7782delAG [p.Gln2594fsX6]). These results highlight some of the pitfalls of genetic analysis in consanguineous families. They also suggest that low birth weight may be a feature of MCPH, a finding that needs confirmation, and confirm that ASPM mutations are associated with simplified cortical gyration.
authors.affiliation: Department of Neurology, Etablissement hospitalier spécialisé de Benaknoun, and Department of Biochemistry, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria.
authors.forename: Abdelkrim
authors.initials: A
authors.lastname: Saadi
authors.forename: Guntram
authors.initials: G
authors.lastname: Borck
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Mohamed Chahine
authors.initials: MC
authors.lastname: Chekkour
authors.forename: Belaïd
authors.initials: B
authors.lastname: Imessaoudene
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.forename: Laurence
authors.initials: L
authors.lastname: Colleaux
authors.forename: Malika
authors.initials: M
authors.lastname: Chaouch