V. Delaurenzi et al., SJOGREN-LARSSON-SYNDROME IS CAUSED BY A COMMON MUTATION IN NORTHERN EUROPEAN AND SWEDISH PATIENTS, Journal of investigative dermatology, 109(1), 1997, pp. 79-83
Sjogren-Larsson syndrome (SLS) is an autosomal recessive disorder char
acterized by congenital ichthyosis, mental retardation, and spastic di
plegia or tetraplegia, Patients with SLS have deficient activity of fa
tty aldehyde dehydrogenase (FALDH), an enzyme involved in long-chain f
atty alcohol oxidation, The cDNA encoding FALDH has recently been clon
ed and several different mutations have been found in SLS patients, We
have now identified a point mutation (C943 --> T) in 7 of 19 kindreds
of European descent, accounting for 24% of the SLS alleles. The C943T
mutation was only found in patients of northern European ancestry fro
m Sweden, the Netherlands, Germany, and Belgium. Haplotype analysis su
ggested that the patients carrying the C943T allele were distantly rel
ated, All four Swedish patients were homozygous for C943T, indicating
that this mutation is probably the major cause of SLS in the inbred Sw
edish families, The mutation leads to the substitution of serine for t
he highly conserved proline 315 in the FALDH protein, and expression s
tudies confirm that it destroys enzymatic activity, The mutation was r
eadily detected with an MulI restriction enzyme digestion test, The fi
nding that C943T is a common SLS mutation in northern European and Swe
dish patients affords a rapid simple method for diagnosing SLS by scre
ening patients for this mutation with DNA-based methods.