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 retardat...

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Bibliographic Details
Published in:European journal of medical genetics 2009-07, Vol.52 (4), p.180-184
Main Authors: Saadi, Abdelkrim, Borck, Guntram, Boddaert, Nathalie, Chekkour, Mohamed Chahine, Imessaoudene, Belaïd, Munnich, Arnold, Colleaux, Laurence, Chaouch, Malika
Format: Article
Language:English
Subjects:
Algeria
ASPM
Biological and medical sciences
Birth Weight
Cerebral Cortex
Cerebral Cortex - abnormalities
Child
Compound heterozygous
Consanguinity
Family
Female
Fundamental and applied biological sciences. Psychology
General aspects. Genetic counseling
Genetics
Genetics of eukaryotes. Biological and molecular evolution
Haplotypes
Heterozygote
Human genetics
Humans
Intellectual Disability
Intellectual Disability - genetics
Life Sciences
Male
Malformations of the nervous system
MCPH5
Medical Education
Medical genetics
Medical sciences
Microcephaly
Microcephaly - diagnostic imaging
Microcephaly - genetics
Mutation
Nerve Tissue Proteins
Nerve Tissue Proteins - genetics
Neurology
Pedigree
Radiography
Siblings
Simplified cortical gyration
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Summary: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.
ISSN:1769-7212
1878-0849
DOI:10.1016/j.ejmg.2009.03.013