Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren-Larsson syndrome

Biagio Didona, Andrea Codispoti, Enrico Bertini, William B Rizzo, Gael Carney, Giovanna Zambruno, Carlo Dionisi-Vici, Mauro Paradisi, Cristina Pedicelli, Gerry Melino, Alessandro Terrinoni

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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 to 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 splice-site mutation (c.471 + 2T > G) in intron 3 and a missense mutation (c.1094C > T; S365L) in exon 7. Analysis of fibroblast RNA by RT-PCR indicated that the splice-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 it 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.

Original languageEnglish (US)
Pages (from-to)865-870
Number of pages6
JournalJournal of Human Genetics
Volume52
Issue number10
DOIs
StatePublished - Oct 1 2007

Fingerprint

Mutation
Exons
long-chain-aldehyde dehydrogenase
Haplotypes
Ichthyosis
Leukoencephalopathies
Insertional Mutagenesis
Missense Mutation
Cerebral Palsy
Heterozygote
Aldehydes
Introns
Fatty Acids
Fibroblasts
RNA
Polymerase Chain Reaction
DNA
Brain
Enzymes
Genes

Keywords

  • Fatty alcohol
  • Fatty aldehyde
  • Ichthyosis
  • Leukotriene
  • Mental retardation
  • Mutation
  • Spastic diplegia
  • ω-Oxidation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Didona, B., Codispoti, A., Bertini, E., Rizzo, W. B., Carney, G., Zambruno, G., ... Terrinoni, A. (2007). Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren-Larsson syndrome. Journal of Human Genetics, 52(10), 865-870. https://doi.org/10.1007/s10038-007-0180-z

Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren-Larsson syndrome. / Didona, Biagio; Codispoti, Andrea; Bertini, Enrico; Rizzo, William B; Carney, Gael; Zambruno, Giovanna; Dionisi-Vici, Carlo; Paradisi, Mauro; Pedicelli, Cristina; Melino, Gerry; Terrinoni, Alessandro.

In: Journal of Human Genetics, Vol. 52, No. 10, 01.10.2007, p. 865-870.

Research output: Contribution to journalArticle

Didona, B, Codispoti, A, Bertini, E, Rizzo, WB, Carney, G, Zambruno, G, Dionisi-Vici, C, Paradisi, M, Pedicelli, C, Melino, G & Terrinoni, A 2007, 'Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren-Larsson syndrome', Journal of Human Genetics, vol. 52, no. 10, pp. 865-870. https://doi.org/10.1007/s10038-007-0180-z
Didona, Biagio ; Codispoti, Andrea ; Bertini, Enrico ; Rizzo, William B ; Carney, Gael ; Zambruno, Giovanna ; Dionisi-Vici, Carlo ; Paradisi, Mauro ; Pedicelli, Cristina ; Melino, Gerry ; Terrinoni, Alessandro. / Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren-Larsson syndrome. In: Journal of Human Genetics. 2007 ; Vol. 52, No. 10. pp. 865-870.
@article{38e348dc43fb47d799a1fb84fe275c42,
title = "Novel and recurrent ALDH3A2 mutations in Italian patients with Sj{\"o}gren-Larsson syndrome",
abstract = "Sj{\"o}gren-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 to 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 splice-site mutation (c.471 + 2T > G) in intron 3 and a missense mutation (c.1094C > T; S365L) in exon 7. Analysis of fibroblast RNA by RT-PCR indicated that the splice-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 it 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.",
keywords = "Fatty alcohol, Fatty aldehyde, Ichthyosis, Leukotriene, Mental retardation, Mutation, Spastic diplegia, ω-Oxidation",
author = "Biagio Didona and Andrea Codispoti and Enrico Bertini and Rizzo, {William B} and Gael Carney and Giovanna Zambruno and Carlo Dionisi-Vici and Mauro Paradisi and Cristina Pedicelli and Gerry Melino and Alessandro Terrinoni",
year = "2007",
month = "10",
day = "1",
doi = "10.1007/s10038-007-0180-z",
language = "English (US)",
volume = "52",
pages = "865--870",
journal = "Journal of Human Genetics",
issn = "1434-5161",
publisher = "Nature Publishing Group",
number = "10",

}

TY - JOUR

T1 - Novel and recurrent ALDH3A2 mutations in Italian patients with Sjögren-Larsson syndrome

AU - Didona, Biagio

AU - Codispoti, Andrea

AU - Bertini, Enrico

AU - Rizzo, William B

AU - Carney, Gael

AU - Zambruno, Giovanna

AU - Dionisi-Vici, Carlo

AU - Paradisi, Mauro

AU - Pedicelli, Cristina

AU - Melino, Gerry

AU - Terrinoni, Alessandro

PY - 2007/10/1

Y1 - 2007/10/1

N2 - 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 to 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 splice-site mutation (c.471 + 2T > G) in intron 3 and a missense mutation (c.1094C > T; S365L) in exon 7. Analysis of fibroblast RNA by RT-PCR indicated that the splice-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 it 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.

AB - 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 to 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 splice-site mutation (c.471 + 2T > G) in intron 3 and a missense mutation (c.1094C > T; S365L) in exon 7. Analysis of fibroblast RNA by RT-PCR indicated that the splice-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 it 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.

KW - Fatty alcohol

KW - Fatty aldehyde

KW - Ichthyosis

KW - Leukotriene

KW - Mental retardation

KW - Mutation

KW - Spastic diplegia

KW - ω-Oxidation

UR - http://www.scopus.com/inward/record.url?scp=34948861078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34948861078&partnerID=8YFLogxK

U2 - 10.1007/s10038-007-0180-z

DO - 10.1007/s10038-007-0180-z

M3 - Article

C2 - 17902024

AN - SCOPUS:34948861078

VL - 52

SP - 865

EP - 870

JO - Journal of Human Genetics

JF - Journal of Human Genetics

SN - 1434-5161

IS - 10

ER -