Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren-Larsson syndrome.
Sjögren-Larsson syndrome (SLS; MIM#270200) is an autosomal recessive neurocutaneous disease caused by mutations in the ALDH3A2 gene for fatty aldehyde dehydrogenase (FALDH), a microsomal enzyme that catalyzes the oxidation of medium- and long- chain aliphatic aldehydes fatty acids. We studied two unrelated Italian SLS patients with ichthyosis, developmental delay, spastic diplegia and brain white matter disease. One patient was homozygous for a novel ALDH3A2 insertion mutation (c.767insA) in exon 5. The other SLS patient was a compound heterozygote for two previously reported mutations: a slice site mutation (c.1094C > T; S365L) in exon 7. Analysis of fibroblast RNA by RT-PCR indicated that the spice-site mutation caused skipping of exons 2 and 3. The c.1094C > T mutation, previously associated with two ALDH3A2 haplotypes, was found on a third distinct haplotype in our patient, which indicates that arose independently in this kindred. These results add to understanding of the genetic basis of SLS and will be useful for DNA diagnosis of this disease.
Didona
Biagio
B
I Dermatology Division, IDI-IRCCS, Via Monti di Creta, 104, Rome, Italy.
Codispoti
Andrea
A
Department of Experimental Medicine, IDI-IRCCS Biochemistry Laboratory, c/o University of Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.
Bertini
Enrico
E
Department of Laboratory Medicine, Unit of Molecular Medicine, Bambino Gesu Hospital, Rome, Italy.
Rizzo
Wiliam B
WB
University of Nebraska Medical Center, Omaha, NE, USA.
Carney
Gael
G
University of Nebraska Medical Center, Omaha, NE, USA.
Zambruno
Giovanna
G
Molecular Biology Laboratory, IDI-IRCCS, Via Monti di Creta, 104, Rome, Italy.
Dionisi-Vici
Carlo
C
Department of Laboratory Medicine, Unit of Molecular Medicine, Bambino Gesu Hospital, Rome, Italy.
Paradisi
Mauro
M
VII Dermatology Division, IDI-IRCCS, Via Monti di Creta, 104, Rome, Italy.
Pedicelli
Cristina
C
VII Dermatology Division, IDI-IRCCS, Via Monti di Creta, 104, Rome, Italy.
Melino
Gerry
G
Department of Experimental Medicine, IDI-IRCCS Biochemistry Laboratory, c/o University of Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. gerry.melino@uniroma2.it.|Medical Research Council, Toxicology Unit, Leicester University, Hodgkin Building, Lancaster Road, P.O. Box 138, Leicester, LE1 9HN, UK. gerry.melino@uniroma2.it.|Mondino-Tor Vergata Center for Experimental Neurobiology, University of Rome Tor Vergata, Rome, Italy. gerry.melino@uniroma2.it.
Terrinoni
Alessandro
A
Department of Experimental Medicine, IDI-IRCCS Biochemistry Laboratory, c/o University of Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. alessandro.terrinoni@uniroma2.it.
D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007558:Italy; D008969:Molecular Sequence Data; D009154:Mutation; D016111:Sjogren-Larsson Syndrome / Q000235:genetics* / Q000473:pathology
D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase