title: Gene and phenotype analysis of congenital generalized lipodystrophy in Japanese: a novel homozygous nonsense mutation in seipin gene.
abstract: Congenital generalized lipodystrophy (CGL), Berardinelli-Seip syndrome, is a rare metabolic disorder characterized by a near total lack of adipose tissue from birth or early infancy. Recently, seipin, encoding a 398-amino acid protein of unknown function, and AGPAT2, encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase 2, were identified as causative genes for CGL. Seipin mutations were found in patients from families originating from Europe and the Middle East. AGPAT2 mutations were found predominantly in African ancestry. However, no information is available on these genes in the pathogenesis of CGL in Asian ancestry. We examined the sequences of the entire coding region of seipin and AGPAT2 in four Japanese CGL patients from independent families. Their average body fat content was 4.7 +/- 0.5%, and the plasma leptin level was 1.15 +/- 0.14 ng/ml. We identified a novel nonsense mutation of seipin at codon 275 (R275X). Of four CGL patients, three were homozygous for R275X. No seipin mutation was found in any exon in one patient. We did not find any AGPAT2 mutations in our Japanese patients, suggesting that AGPAT2 is a minor causative gene, if any, for CGL in Japanese. This is the first report on gene and phenotype analysis of CGL in Japanese.
authors.affiliation: Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan. kebihara@kuhp.kyoto-u.ac.jp
authors.forename: Ken
authors.initials: K
authors.lastname: Ebihara
authors.forename: Toru
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Masuzaki
authors.forename: Nozomi
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hideki
authors.initials: H
authors.lastname: Chusho
authors.forename: Fumiko
authors.initials: F
authors.lastname: Miyanaga
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyazawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hayashi
authors.forename: Kiminori
authors.initials: K
authors.lastname: Hosoda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Kazuwa
authors.initials: K
authors.lastname: Nakao
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D003062:Codon; D018389:Codon, Nonsense; D005260:Female; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008060:Lipodystrophy / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D010641:Phenotype
chemical_list: C432679:BSCL2 protein, human; D003062:Codon; D018389:Codon, Nonsense; D044388:GTP-Binding Protein gamma Subunits