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J Med Genet 48:136-140 doi:10.1136/jmg.2010.082206
  • Short report

Cohen syndrome diagnosis using whole genome arrays

  1. Maja Hempel1,9
  1. 1Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
  2. 2Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany
  3. 3Department of Pediatrics, Ludwig-Maximilians-Universität, Munich, Germany
  4. 4Department of Pediatrics, Josefinum Augsburg, Augsburg, Germany
  5. 5Institute of Human Genetics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany
  6. 6Max Planck Institute for Molecular Genetics, Department Human Molecular Genetics, Berlin, Germany
  7. 7Private Clinic B.Prager & A.Junge, Dresden, Germany
  8. 8Institute of Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
  9. 9Institute of Human Genetics, Technische Universität München, Munich, Germany
  1. Correspondence to Dr Maja Hempel, Institute of Human Genetics, Technische Universität München, Trogerstraße 32, D-81675 Munich, Germany; hempel{at}humangenetik.med.tu-muenchen.de
  • Received 21 June 2010
  • Revised 12 August 2010
  • Accepted 17 August 2010
  • Published Online First 4 October 2010

Abstract

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.

Footnotes

  • Funding NGFN Geschäftsstelle; c/o Deutsches Krebsforschungszentrum - DKFZIm Neuenheimer Feld 580, V025; 69120 Heidelberg. Other funders: BMBF, Germany.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Approval for the study had been obtained by the ethical review boards of the participating institutions.

  • Provenance and peer review Not commissioned; externally peer reviewed.