Novel Mutation in Sjögren-Larsson Syndrome Is Associated With Divergent Neurologic Phenotypes

The study identified a novel c.1309A>T mutation in the ALDH3A2 gene in two unrelated Honduran patients with Sjögren-Larsson syndrome, who exhibited significantly different neurologic phenotypes despite having the same genetic mutation. One patient had spastic quadriplegia with neuroregression, while the other had a static form of spastic diplegia with neurodevelopmental disabilities. Both patients showed a profound deficiency in fatty aldehyde dehydrogenase activity and impaired fatty alcohol metabolism. The findings suggested that the variation in neurologic phenotype was influenced by unidentified epigenetic/environmental factors, gene modifiers, or other mechanisms, rather than the ALDH3A2 mutation alone, highlighting the complexity of genotype-phenotype correlations in Sjögren-Larsson syndrome.