Genetic assessment of ten Egyptian patients with Sjögren-Larsson syndrome: expanding the clinical spectrum and reporting a novel ALDH3A2 mutation.

Assessment of ten Egyptian patients with Sjögren-Larsson syndrome (SLS) detected; unusual clinical manifestations, a first report of brain atrophy in SLS, some patients exhibited neither retinal dots nor white matter changes previously reported as essential manifestations. We identified five mutations in ALDH3A2 gene including a novel one and suggest a founder effect. Sjögren-Larsson syndrome is a rare autosomal recessive inborn error of lipid metabolism caused by mutations in the ALDH3A2 gene that codes for fatty aldehyde dehydrogenase and result in a triad of ichthyosis, spasticity, and mental retardation. Clinical, radiological, biochemical, and neurophysiological evaluation in ten SLS patients descending from seven unrelated Egyptian pedigrees was followed by Sanger sequencing of ALDH3A2 performed by ABI 3500. All patients presented with SLS triad; ichthyosis, spasticity of four limbs and hyperreflexia with an intelligent quotient (IQ) ranging from (39 to 69). Other manifestations were dysmorphic features, seizures, and skeletal and ophthalmological affection. Mutational analysis of ALDH3A2 gene revealed three missense, one splice site, and one novel stop codon mutation; c.991G>T (p.E331X). Biochemical studies showed decrease of fatty aldehyde dehydrogenase activity. Our results reinforce the distinct clinical, radiological, and biochemical features of ALDH3A2-related SLS which are the clue for targeted molecular testing. Moreover, we present additional unreported clinical findings and a novel mutation thus expanding the phenotypic and mutational spectrum of this rare disorder.