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European Journal of Human Genetics (2009) 17, 1076 1079 & 2009 Macmillan Publishers Limited All rights reserved 1018-4813/09 $32.00
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A novel VPS13B mutation in two brothers with Cohen syndrome, cutis verticis gyrata and sensorineural deafness
Andr Mgarban1,2, Rima Slim3, Gudrun Nrnberg4, Inga Ebermann5, Peter Nrnberg4,6
and Hanno Jrn Bolz*,5
1Unit de Gntique Mdicale, Facult de Mdecine, Universit Saint-Joseph, Beirut, Lebanon; 2Institut Jrme Lejeune, Paris, France; 3Departments of Human Genetics and Obstetrics Gynecology, McGill University Health Centre, Montreal, Quebec, Canada; 4Cologne Center for Genomics and Institute for Genetics, University of Cologne, Cologne, Germany;
5Institute of Human Genetics, University of Cologne, Cologne, Germany; 6Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany
We have earlier described a syndrome characterized by microcephaly, cutis verticis gyrata, retinitis pigmentosa, cataracts, hearing loss and mental retardation (Mendelian inheritance in man (MIM) no: 605685) in two brothers from a non-consanguineous Lebanese family. In view of the rarity of the disorder and the high rate of inbreeding in the Lebanese population, we assumed an autosomal recessive trait inherited from a common ancestor. A genomewide scan was performed. The single locus on the long arm of chromosome 8 that showed homozygosity by descent comprised the gene responsible for Cohen syndrome (CS), VPS13B. We then sequenced VPS13B in the patients and found a homozygous splice site mutation. Several possible explanations for the overlap between CS and the clinical features observed in our patients are discussed. Our data highlight the potential of high-resolution homozygosity mapping in small populations with a high rate of inbreeding.
European Journal of Human Genetics (2009) 17, 10761079; doi:http://dx.doi.org/10.1038/ejhg.2008.273
Web End =10.1038/ejhg.2008.273 ; published online 4 February 2009
Keywords: VPS13B; Cohen syndrome; cutis verticis gyrata
IntroductionMental retardation affects 13% of the general population,1 but only 37% can be recognized as defined syndromes. In as many as 3050%, the cause is unknown.2
In 2001, we described a Lebanese family with syndromic mental retardation in two brothers. They exhibited microcephaly, primary cutis verticis gyrata of the scalp, prominent supraorbital ridges, coarse facial features (large
nose, hypertelorism), retinitis pigmentosa, cataracts, sensorineural hearing loss and kyphoscoliosis in addition to mental retardation.3 As this combination of symptoms did not fit any known clinical...