Cohen syndrome diagnosis using whole genome arrays

Nuria Rivera-Brugués (1) , Beate Albrecht (2) , Dagmar Wieczorek (2) , Heinrich Schmidt (3) , Thomas Keller (4) , Ina Göhring (5) , Arif B. Ekici (5) , Andreas Tzschach (6) , Masoud Garshasbi (6) , Kathlen Franke (7) , Norman Klopp (8) , H. Erich Wichmann (8) , Thomas Meitinger (8) , Tim M. Strom (8) , Maja Hempel (8)

1 Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg
2 Institut für Humangenetik, Universitätsklinikum Essen, Essen
3 Department of Pediatrics, Ludwig-Maximilians-Universität, Munich
4 Department of Pediatrics, Josefinum Augsburg, Augsburg
5 Institute of Human Genetics [Erlangen, Allemagne]
6 Department Human Molecular Genetics [MPIMG Berlin]
7 Private Clinic B.Prager & A.Junge, Dresden
8 N/A

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 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 . We have analysed high density oligonucleotide array data from patients with unexplained mental retardation (n=1523) and normal controls (n=1612) for copy number variation (CNV) changes. We detected intragenic heterozygous deletions in the gene in three patients but no such changes in the controls. Subsequent sequencing of the gene revealed point mutations in the second allele in all three patients analysed. Genome wide CNV screening with high density arrays provides a tool to detect intragenic deletions in the gene. We present an example how microarrays can be used to identify autosomal recessive syndromes and to extend the phenotypic and mutational spectrum of recessive disorders.

Mots clés: Diagnostics; Clinical genetics; Genetic screening/counselling; Molecular genetics; Neurology

Nuria Rivera-Brugués, Beate Albrecht, Dagmar Wieczorek, Heinrich Schmidt, Thomas Keller, et al.. Cohen syndrome diagnosis using whole genome arrays. Journal of Medical Genetics, 2010, 48 (2), pp.136. ⟨10.1136/jmg.2010.082206⟩. ⟨hal-00573454⟩