Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome

Am J Hum Genet. 2001 Nov;69(5):1002-12. doi: 10.1086/324121. Epub 2001 Oct 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Esterases / genetics*
  • Exons / genetics
  • Female
  • Genetic Linkage / genetics*
  • Haplotypes
  • Humans
  • Introns / genetics
  • Linkage Disequilibrium / genetics
  • Lipase / chemistry
  • Lipase / genetics*
  • Male
  • Molecular Sequence Data
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / genetics
  • Mutation / genetics*
  • Physical Chromosome Mapping
  • Protein Conformation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Syndrome


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

Associated data

  • GENBANK/AC006055
  • GENBANK/AF151816
  • GENBANK/AL606838
  • GENBANK/X87485
  • OMIM/230900
  • OMIM/242300
  • OMIM/266500
  • OMIM/270200
  • OMIM/272200
  • OMIM/2753630
  • OMIM/302960
  • OMIM/308100
  • OMIM/604780