title: Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.
abstract: Chanarin-Dorfman syndrome (CDS) is a rare autosomal recessive form of nonbullous congenital ichthyosiform erythroderma (NCIE) that is characterized by the presence of intracellular lipid droplets in most tissues. We previously localized a gene for a subset of NCIE to chromosome 3 (designated "the NCIE2 locus"), in six families. Lipid droplets were found in five of these six families, suggesting a diagnosis of CDS. Four additional families selected on the basis of a confirmed diagnosis of CDS also showed linkage to the NCIE2 locus. Linkage-disequilibrium analysis of these families, all from the Mediterranean basin, allowed us to refine the NCIE2 locus to an approximately 1.3-Mb region. Candidate genes from the interval were screened, and eight distinct mutations in the recently identified CGI-58 gene were found in 13 patients from these nine families. The spectrum of gene variants included insertion, deletion, splice-site, and point mutations. The CGI-58 protein belongs to a large family of proteins characterized by an alpha/beta hydrolase fold. CGI-58 contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. Interestingly, CGI-58 differs from other members of the esterase/lipase/thioesterase subfamily in that its putative catalytic triad contains an asparagine in place of the usual serine residue.
authors.affiliation: Centre National de Génotypage, 91057 Evry Cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Lefèvre
authors.forename: F
authors.initials: F
authors.lastname: Jobard
authors.forename: F
authors.initials: F
authors.lastname: Caux
authors.forename: B
authors.initials: B
authors.lastname: Bouadjar
authors.forename: A
authors.initials: A
authors.lastname: Karaduman
authors.forename: R
authors.initials: R
authors.lastname: Heilig
authors.forename: H
authors.initials: H
authors.lastname: Lakhdar
authors.forename: A
authors.initials: A
authors.lastname: Wollenberg
authors.forename: J L
authors.initials: JL
authors.lastname: Verret
authors.forename: J
authors.initials: J
authors.lastname: Weissenbach
authors.forename: M
authors.initials: M
authors.lastname: Ozgüc
authors.forename: M
authors.initials: M
authors.lastname: Lathrop
authors.forename: J F
authors.initials: JF
authors.lastname: Prud'homme
authors.forename: J
authors.initials: J
authors.lastname: Fischer
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D000293:Adolescent; D000328:Adult; D020816:Amino Acid Motifs; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics*; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D004950:Esterases / Q000737:chemistry / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium / Q000235:genetics; D008049:Lipase / Q000737:chemistry / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D020161:Physical Chromosome Mapping; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
chemical_list: D009097:Multienzyme Complexes; D012333:RNA, Messenger; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C439972:ABHD5 protein, human; D004950:Esterases; D008049:Lipase