SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly

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Item Type:	Article
Title:	SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly
Creators Name:	Garshasbi, M., Motazacker, M.M., Kahrizi, K., Behjati, F., Abedini, S.S., Nieh, S.E., Firouzabadi, S.G., Becker, C., Rueschendorf, F., Nuernberg, P., Tzschach, A., Vazifehmand, R., Erdogan, F., Ullmann, R., Lenzner, S., Kuss, A.W., Ropers, H.H. and Najmabadi, H.
Abstract:	Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based homozygosity mapping and high-resolution microarray-based comparative genomic hybridization (array CGH) revealed a deletion of approximately 150-200 kb, encompassing the promoter and the first six exons of the MCPH1 gene, one out of four genes that have been previously implicated in ARMR with microcephaly. Reexamination of affected individuals revealed a high proportion of prematurely condensed chromosomes, which is a hallmark of this condition, but in spite of the severity of the mutation, all patients showed only borderline to mild microcephaly. Therefore the phenotypic spectrum of MCPH1 mutations may be wider than previously assumed, with ARMR being the only consistent clinical finding.
Keywords:	Chromosome Mapping, Consanguinity, Family, Gene Deletion, Homozygote, Intellectual Disability, Microarray Analysis, Microcephaly, Nerve Tissue Proteins, Pedigree, Recessive Genes, Single Nucleotide Polymorphism
Source:	Human Genetics
ISSN:	0340-6717
Publisher:	Springer
Volume:	118
Number:	6
Page Range:	708-715
Date:	February 2006
Official Publication:	https://doi.org/10.1007/s00439-005-0104-y
PubMed:	View item in PubMed

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