Compound heterozygous ASPM mutations associated with microcephaly and simplified cortical gyration in a consanguineous Algerian family.
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.
Saadi
Abdelkrim
A
Department of Neurology, Etablissement hospitalier spécialisé de Benaknoun, and Department of Biochemistry, Centre Hospitalo-Universitaire Mustapha Bacha, Algiers, Algeria.
Borck
Guntram
G
Boddaert
Nathalie
N
Chekkour
Mohamed Chahine
MC
Imessaoudene
Belaïd
B
Munnich
Arnold
A
Colleaux
Laurence
L
Chaouch
Malika
M