Novel mutation in Sjogren-Larsson syndrome is associated with divergent neurologic phenotypes

Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/q...

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Published inJournal of child neurology Vol. 28; no. 10; p. 1259
Main Authors Davis, Kathleen, Holden, Kenton R, S'Aulis, Dana, Amador, Claudia, Matheus, M Gisele, Rizzo, William B
Format Journal Article
LanguageEnglish
Published United States 01.10.2013
Subjects
Aldehyde Oxidoreductases - genetics
Aldehyde Oxidoreductases - metabolism
Child, Preschool
Female
Fibroblasts - metabolism
Humans
Ichthyosis - genetics
Ichthyosis - metabolism
Lipid Metabolism - genetics
Male
Mutation
Phenotype
Severity of Illness Index
Sjogren-Larsson Syndrome - genetics
Sjogren-Larsson Syndrome - metabolism
phenotype
mutation
aldehyde dehydrogenase
fatty alcohol
Sjögren-Larsson
spasticity
ichthyosis
neurologic
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Summary:Sjögren-Larsson syndrome is an inherited disorder of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase, which results in accumulation of fatty aldehydes and alcohols and is characterized by ichthyosis, intellectual disability, and spastic diplegia/quadriplegia. The authors describe 2 unrelated Honduran patients who carried the same novel homozygous nonsense mutation (c.1309A>T, p.K437X) and ALDH3A2 DNA haplotype, but widely differed in disease severity. One patient exhibited spastic quadriplegia with unusual neuroregression, whereas the other patient had the usual static form of spastic diplegia with neurodevelopmental disabilities. Biochemical analyses showed a similar profound deficiency of fatty aldehyde dehydrogenase activity and impaired fatty alcohol metabolism in both patients' cultured fibroblasts. These results indicate that variation in the neurologic phenotype of Sjögren-Larsson syndrome is not strictly determined by the ALDH3A2 mutation or the biochemical defect as expressed in cultured fibroblasts, but by unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms.
ISSN:1708-8283
DOI:10.1177/0883073812460581