An autosomal recessive syndrome of severe mental retardation, cataract, coloboma and kyphosis maps to the pericentromeric region of chromosome 4.
We report on three siblings with a novel mental retardation (MR) syndrome who were born to distantly related Iranian parents. The clinical problems comprised severe MR, cataracts with onset in late adolescence, kyphosis, contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. Two patients also had uni- or bilateral iris coloboma. Linkage analysis revealed a single 10.4 Mb interval of homozygosity with significant LOD score in the pericentromeric region of chromosome 4 flanked by SNPs rs728293 (4p12) and rs1105434 (4q12). This interval contains more than 40 genes, none of which has been implicated in MR so far. The identification of the causative gene defect for this syndrome will provide new insights into the development of the brain and the eye.
Kahrizi
Kimia
K
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
Najmabadi
Hossein
H
Kariminejad
Roxana
R
Jamali
Payman
P
Malekpour
Mahdi
M
Garshasbi
Masoud
M
Ropers
Hans Hilger
HH
Kuss
Andreas Walter
AW
Tzschach
Andreas
A
D002386:Cataract / Q000235:genetics*; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D003103:Coloboma / Q000235:genetics*; D005190:Family; D005260:Female; D005808:Genes, Recessive; D006239:Haplotypes; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007738:Kyphosis / Q000235:genetics*; D008126:Lod Score; D008297:Male; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013577:Syndrome
Am J Hum Genet. 2006 Sep;79(3):562-6
16909395
Hum Genet. 2004 Sep;115(4):302-9
15257456
Hum Genet. 2007 Mar;121(1):43-8
17120046
Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8696-9
1717985
Nat Genet. 1995 Nov;11(3):257-65
7581448
Hum Genet. 2006 Feb;118(6):708-15
16311745
J Med Genet. 1988 Jan;25(1):41-3
3351890
Nat Genet. 2005 Mar;37(3):221-3
15696165
Nat Biotechnol. 2003 Oct;21(10):1233-7
12960966
Am J Hum Genet. 2006 Apr;78(4):702-7
16532399
Genes Chromosomes Cancer. 2002 Mar;33(3):295-303
11807987
Am J Ment Retard. 2005 Jul;110(4):253-67
15941363
Genome Res. 2004 Mar;14(3):414-25
14993208
Ment Retard Dev Disabil Res Rev. 2002;8(3):117-34
12216056