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

Journal of Child Neurology
Kathleen DavisW B Rizzo

Abstract

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.

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Citations

Oct 30, 2018·Human Mutation·Maximilian WeustenfeldMarkus A Keller
Sep 3, 2019·Molecular Genetics & Genomic Medicine·Jihye ParkDae-Hyun Jang
Sep 16, 2017·Journal of Perinatal Medicine·Pippa StapsMichèl A A P Willemsen
May 13, 2020·JIMD Reports·Pippa StapsMichèl A A P Willemsen
Aug 23, 2016·Expert Opinion on Orphan Drugs·William B Rizzo
Oct 11, 2020·Paediatric Anaesthesia·Marcellene H FranzenWilliam B Rizzo
Jul 29, 2021·Journal of Child Neurology·Simone WarrackWilliam B Rizzo

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