title: An Indian family with Sjögren-Larsson syndrome caused by a novel ALDH3A2 mutation.
abstract: Sjögren-Larsson syndrome is an autosomal-recessive hereditary disorder characterized by congenital ichthyosis, mental retardation and spastic diplegia or tetraplegia. It is known that mutations in the fatty aldehyde dehydrogenase (FALDH) gene (ALDH3A2) underlie SLS. We report two Indian sisters showing typical clinical features of SLS. Direct sequencing of the entire coding region of ALDH3A2 revealed a novel homozygous mutation, c.142G>T (p.Asp48Tyr) in exon 1, in both patients. Their parents harbored the mutation heterozygously. Mutant-allele-specific amplification analysis using PCR products as a template verified the mutation in the patients. The aspartic acid residue at the mutation site is located in the C-terminal portion of the second a-helix strand, a2, of N-terminal four helices of FALDH and the FALDH amino-acid sequence alignment shows that this aspartic acid residue is conserved among several diverse species. Until now, a number of mutations in ALDH3A2 have been shown to be responsible for SLS in Europe, the Middle East, Africa, and North and South America. However, in Asian populations, ALDH3A2 mutations have been identified only in Japanese SLS patients. Here we report an ALDH3A2 mutation for the first time in SLS patients in the Asian country other than Japan. The present results suggest that ALDH3A2 is a gene responsible for SLS in Asian populations. We hope ALDH3A2 mutation search will be globally available including many Asian countries in the future.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sakai
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Teruki
authors.initials: T
authors.lastname: Yanagi
authors.forename: Sheela
authors.initials: S
authors.lastname: Nampoothiri
authors.forename: Tony
authors.initials: T
authors.lastname: Mampilly
authors.forename: V
authors.initials: V
authors.lastname: Sunitha
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002675:Child, Preschool; D005091:Exons; D005260:Female; D006801:Humans; D007223:Infant; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D051381:Rats; D016415:Sequence Alignment; D016111:Sjogren-Larsson Syndrome / Q000175:diagnosis / Q000235:genetics*
chemical_list: D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase