RT Journal Article
SR Electronic
T1 Cohen syndrome diagnosis using whole genome arrays
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 136
OP 140
DO 10.1136/jmg.2010.082206
VO 48
IS 2
A1 Nuria Rivera-Brugués
A1 Beate Albrecht
A1 Dagmar Wieczorek
A1 Heinrich Schmidt
A1 Thomas Keller
A1 Ina Göhring
A1 Arif B Ekici
A1 Andreas Tzschach
A1 Masoud Garshasbi
A1 Kathlen Franke
A1 Norman Klopp
A1 H-Erich Wichmann
A1 Thomas Meitinger
A1 Tim M Strom
A1 Maja Hempel
YR 2011
UL http://jmg.bmj.com/content/48/2/136.abstract
AB Background Cohen syndrome is a rare autosomal recessive disorder with a complex phenotype including psychomotor retardation, microcephaly, obesity with slender extremities, joint laxity, progressive chorioretinal dystrophy/myopia, intermittent isolated neutropenia, a cheerful disposition, and characteristic facial features. The COH1 gene, which contains 62 exons, is so far the only gene known to be associated with Cohen syndrome. Point mutations, deletions and duplications have been described in this gene. Oligonucleotide arrays have reached a resolution which allows the detection of intragenic deletions and duplications, especially in large genes such as COH1.Method and results High density oligonucleotide array data from patients with unexplained mental retardation (n=1523) and normal controls (n=1612) were analysed for copy number variation (CNV) changes. Intragenic heterozygous deletions in the COH1 gene were detected in three patients but no such changes were detected in the controls. Subsequent sequencing of the COH1 gene revealed point mutations in the second allele in all three patients analysed.Conclusion Genome-wide CNV screening with high density arrays provides a tool to detect intragenic deletions in the COH1 gene. This report presents an example of how microarrays can be used to identify autosomal recessive syndromes and to extend the phenotypic and mutational spectrum of recessive disorders.