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: C Lefèvre, F Jobard, F Caux, B Bouadjar, A Karaduman, R Heilig, H Lakhdar, A Wollenberg, J L Verret, J Weissenbach, M Ozgüc, M Lathrop, J F Prud'homme, J Fischer
• Journal: American journal of human genetics (Am J Hum Genet) Vol. 69 Issue 5 Pg. 1002-12 (Nov 2001) ISSN: 0002-9297 [Print] United States
• PMID: 11590543 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Multienzyme Complexes
• RNA, Messenger
• 1-Acylglycerol-3-Phosphate O-Acyltransferase
• ABHD5 protein, human
• Esterases
• Lipase

Topics

• 1-Acylglycerol-3-Phosphate O-Acyltransferase
• Adolescent
• Adult
• Amino Acid Motifs
• Base Sequence
• Child
• Child, Preschool
• Chromosomes, Human, Pair 3 (genetics)
• Conserved Sequence
• DNA Mutational Analysis
• Esterases (chemistry, genetics)
• Exons (genetics)
• Female
• Genetic Linkage (genetics)
• Haplotypes
• Humans
• Introns (genetics)
• Linkage Disequilibrium (genetics)
• Lipase (chemistry, genetics)
• Male
• Molecular Sequence Data
• Multienzyme Complexes (chemistry, genetics)
• Mutation (genetics)
• Physical Chromosome Mapping
• Protein Conformation
• RNA, Messenger (genetics, metabolism)
• Syndrome