SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly.
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.
Garshasbi
Masoud
M
Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.
Motazacker
Mohammad Mahdi
MM
Kahrizi
Kimia
K
Behjati
Farkhondeh
F
Abedini
Seyedeh Sedigheh
SS
Nieh
Sahar Esmaeeli
SE
Firouzabadi
Saghar Ghasemi
SG
Becker
Christian
C
Rüschendorf
Franz
F
Nürnberg
Peter
P
Tzschach
Andreas
A
Vazifehmand
Reza
R
Erdogan
Fikret
F
Ullmann
Reinhard
R
Lenzner
Steffen
S
Kuss
Andreas W
AW
Ropers
H Hilger
HH
Najmabadi
Hossein
H
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
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins