A Common Deletion Mutation in European Patients with Sjögren-Larsson Syndrome

Abstract

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder characterized by ichthyosis, mental retardation, spasticity, and deficient activity of fatty aldehyde dehydrogenase (FALDH). We identified a frequent FALDH mutation in exon 9 among SLS probands of European descent. This mutation is a 2-bp deletion of nucleotides GA 1297–1298 and results in premature termination of translation at codon 435 along with substitution of Arg and Cys for Glu433and Gly434, respectively. The GA del1297–8mutation was found in 10 of 21 European SLS probands and could be readily detected using an allele-specific PCR method. This GA deletion mutation or a previously identified common point mutation (C943T) was present in 66% of the European SLS probands, and the two mutations together accounted for 48% of the SLS alleles. Screening European patients for these two common mutations should be useful for DNA-based diagnosis of SLS and genetic counseling.