Molecular Analysis of Berardinelli-Seip Congenital Lipodystrophy in Oman

Molecular Analysis of Berardinelli-Seip Congenital Lipodystrophy in Oman Evidence for Multiple Loci Kirsten Heathcote 1 , Anna Rajab 2 , Jocelyne Magré 3 , Petros Syrris 1 , Mehran Besti 1 , Michael Patton 1 , Marc Délépine 4 , Mark Lathrop 4 , Jacqueline Capeau 3 and Steve Jeffery 1 1 Medical Genetics Unit, Department of Child Health, St. George’s Hospital Medical School, London, U.K. 2 Medical Genetics Unit, Directorate General of Health Affairs, Ministry of Health, Muscat, Oman 3 Faculté de Médecine Saint-Antoine, Université Pierre et Marie Curie, Paris, France 4 Centre National de Génotypage, Paris, France Abstract Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by the absence of body fat and insulin resistance and accompanied by other features, including acanthosis nigricans, organomegaly, hyperandrogenism, and diabetes. We have examined case subjects from 11 families in Oman with CGL. All subjects were the progeny of consanguineous marriages; therefore, a homozygosity mapping strategy was used to investigate the reported loci, 11q13 and 9q34. Three subjects could be linked to 11q13, and mutations were found within the seipin gene. An additional eight subjects were linked to 9q34, but the locus was in a 9-cM interval with no known microsatellites, so further fine mapping was not possible. However, two sibships (four subjects) did not map to either locus, raising the possibility of more than two lipodystrophy loci within the Oman population. Footnotes Address correspondence and reprint requests to Steve Jeffery, Medical Genetics Unit, Department of Child Health, St. George’s Hospital Medical School, Cranmer Terrace, Tooting, London, SW17 0RE U.K. E-mail: sggt100{at}sghms.ac.uk . Received for publication 21 September 2000 and accepted in revised form 15 January 2002. K.H. and A.R. contributed equally to this study. CGL, congenital generalized lipodystrophy; SNP, single nucleotide polymorphism. DIABETES