title: A gene for congenital generalized lipodystrophy maps to human chromosome 9q34.
abstract: Congenital generalized lipodystrophy (CGL, Berardinelli-Seip Syndrome, OMIM # 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (theta(max) = 0.05). There was evidence for genetic heterogeneity (alpha = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL1 critical region harbors a plausible candidate gene encoding the retinoid X receptor alpha (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue.
authors.affiliation: Department of Internal Medicine, and Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, 75235, USA. agarg@mednet.swmed.edu
authors.forename: A
authors.initials: A
authors.lastname: Garg
authors.forename: R
authors.initials: R
authors.lastname: Wilson
authors.forename: R
authors.initials: R
authors.lastname: Barnes
authors.forename: E
authors.initials: E
authors.lastname: Arioglu
authors.forename: Z
authors.initials: Z
authors.lastname: Zaidi
authors.forename: F
authors.initials: F
authors.lastname: Gurakan
authors.forename: N
authors.initials: N
authors.lastname: Kocak
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: S I
authors.initials: SI
authors.lastname: Taylor
authors.forename: S B
authors.initials: SB
authors.lastname: Patel
authors.forename: A M
authors.initials: AM
authors.lastname: Bowcock
mesh_terms: D000052:Acanthosis Nigricans / Q000235:genetics; D017667:Adipocytes; D000293:Adolescent; D002454:Cell Differentiation; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003241:Consanguinity; D003920:Diabetes Mellitus / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000235:genetics; D007333:Insulin Resistance / Q000235:genetics; D008060:Lipodystrophy / Q000151:congenital* / Q000235:genetics*; D008126:Lod Score; D008297:Male; D010375:Pedigree; D018168:Receptors, Retinoic Acid / Q000235:genetics; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics
chemical_list: D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors