title: SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly.
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.
authors.affiliation: Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
authors.forename: Masoud
authors.initials: M
authors.lastname: Garshasbi
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Motazacker
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
authors.forename: Farkhondeh
authors.initials: F
authors.lastname: Behjati
authors.forename: Seyedeh Sedigheh
authors.initials: SS
authors.lastname: Abedini
authors.forename: Sahar Esmaeeli
authors.initials: SE
authors.lastname: Nieh
authors.forename: Saghar Ghasemi
authors.initials: SG
authors.lastname: Firouzabadi
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
authors.forename: Franz
authors.initials: F
authors.lastname: Rüschendorf
authors.forename: Peter
authors.initials: P
authors.lastname: Nürnberg
authors.forename: Andreas
authors.initials: A
authors.lastname: Tzschach
authors.forename: Reza
authors.initials: R
authors.lastname: Vazifehmand
authors.forename: Fikret
authors.initials: F
authors.lastname: Erdogan
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.forename: Steffen
authors.initials: S
authors.lastname: Lenzner
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Kuss
authors.forename: H Hilger
authors.initials: HH
authors.lastname: Ropers
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
mesh_terms: D000293:Adolescent; D000328:Adult; D018797:Cell Cycle Proteins; D002874:Chromosome Mapping / Q000379:methods*; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D005190:Family; D005260:Female; D017353:Gene Deletion; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis / Q000379:methods*; D008831:Microcephaly / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins