Funding sources None.
An exceptional mutational event leading to Chanarin–Dorfman syndrome in a large consanguineous family
Article first published online: 13 MAY 2011
© 2011 The Authors. BJD © 2011 British Association of Dermatologists
British Journal of Dermatology
Volume 164, Issue 6, pages 1390–1392, June 2011
How to Cite
Samuelov, L., Fuchs-Telem, D., Sarig, O. and Sprecher, E. (2011), An exceptional mutational event leading to Chanarin–Dorfman syndrome in a large consanguineous family. British Journal of Dermatology, 164: 1390–1392. doi: 10.1111/j.1365-2133.2011.10252.x
Conflicts of interest None declared.
L.S. and D.F.-T. contributed equally to this study.
- Issue published online: 25 MAY 2011
- Article first published online: 13 MAY 2011
- Accepted manuscript online: 17 FEB 2011 08:23AM EST
- Accepted for publication 4 February 2011
Chanarin–Dorfman syndrome (CDS) is a rare autosomal recessive metabolic disorder featuring congenital ichthyosis combined with pleiomorphic visceral manifestations associated with tissue accumulation of cytoplasmic lipid droplets. Mutations in the ABHD5 gene, encoding a crucial cofactor for adipose triglyceride lipase, have been found to underlie all CDS cases reported to date. The purposed of this study was to ascertain the genetic defect underlying CDS in a large multigenerational family. We used a combination of direct sequencing, reverse transcriptase–polymerase chain reaction (RT-PCR) and microsatellite marker genotyping to identify a novel CDS-causing mutation in ABHD5. Although no pathogenic mutation could be identified in the coding sequence of the ABHD5 gene, polymorphic marker genotyping analysis supported linkage to this gene locus. Accordingly, direct sequencing of RT-PCR amplification products generated from patient skin-derived total RNA, revealed in all four patients the presence of a 101 bp insertion between exon 3 and exon 4. Bioinformatic analysis and direct sequencing indicated that this insertion resulted from an exceptional mutational event, namely, the insertion of a LINE element into intron 3 of the ABHD5 gene, leading to aberrant splicing out of the mutant intron 3. Our results confirm genetic homogeneity in CDS and underscore the importance of RNA studies in the molecular diagnosis of genodermatoses.