Sjögren–Larsson syndrome (SLS), a rare autosomal disorder
characterized by ichthyosis, spastic
neurological disorders and oligophrenia, is associated with deficiency of
fatty aldehyde dehydrogenase encoded by a gene on chromosome 17q11.2. Mutations
of the gene (GDB symbol
ALDH10) were recently identified in three SLS patients. Another
aldehyde dehydrogenase isozyme,
ALDH3, also has a high activity for fatty aldehyde oxidation, and is encoded
by a gene in
chromosome 17q11.2. Abnormality of the ALDH3 gene could also cause
a similar syndrome.
The examination of the ALDH3 locus of three additional SLS
patients showed that two are
heterozygous with C→G at nt 985 (Pro→Ala at protein position 329).
However, the mutation was
found to be common (frequency of the atypical allele is about 0·25)
in normal subjects, and not related to SLS.
Isoelectric focusing analysis indicated that ALDH3 is hardly expressed
in normal as well as
patients' fibroblast cells, while ALDH10 expressed in the normal cells
is diminished in the three
patients' cells. The level of ALDH10 mRNA is also low in the
The examination of the ALDH10 locus revealed the existence of a
3 base deletion coupled with a
21 base insertion at intron 6/exon 7 junction in one patient. This
abnormality is the same as that
found in the patient previously reported by other investigators.
One patient is associated with a 2
base deletion at nt 1297 and consequent premature chain termination
at protein position 434.
Another patient is a compound heterozygote for the same 2 base deletion
at nt 1297 and a 5 base
insertion at nt 1311 and premature chain termination at protein
position 457. Unique characteristics
of the SLS mutations are pointed out.