Researchers have conducted the first-ever clinico-genetic study on Egyptian patients affected by Wolman disease (WD), shedding new light on this severe subtype of lysosomal acid lipase deficiency (LAL-D).
The study revealed 3 homozygous disease-causing variants located in the LIPA gene. One of them was identified as a novel missense variant (NM_000235.4: c.1122 T > G; p. His374Gln) and was classified as a likely pathogenic variant. All the identified variants were predicted to have disease-causing potential through in silico analyses.
“Our findings expand the spectrum of variants involved in WD which may help to investigate phenotype-genotype correlation and assist genetic counseling. To the best of our knowledge, this is the first clinico-genetic study carried out on Egyptian patients affected with WD,” the researchers wrote in the Journal of Molecular Neuroscience.
Apart from the novel missense variant detected in exon 10 of the LIPA gene, the researchers also discovered another variant (c.1055_1057del; p. Asp352del) affecting the same exon, found in 2 patients.
Read more about LAL-D etiology
In addition, a homozygous substitution (c.260G > T) in exon 4 of the LIPA gene was identified in 4 patients from 2 separate families.
The study enrolled 7 patients from 5 unrelated Egyptian families who received their diagnoses between 2 and 6 months of age. They presented severe clinical signs of the disease, including abdominal distension, hepatomegaly, splenomegaly, gastrointestinal disturbances, anemia, adrenal calcification, and premature death.
Moreover, all patients had abnormal serum lipid profiles, hypercholesterolemia, and elevated transaminase levels.
Initially, patients were screened using targeted next-generation sequencing. The researchers then analyzed the cosegregation of causative variants through Sanger sequencing and performed multiple in silico analyses to assess the pathogenicity of the identified candidate variants.
Elaraby NM, Galal ER, Abdel-Hamid M, et al. First LIPA mutational analysis in Egyptian patients reveals one novel variant: Wolman disease. J Mol Neurosci. Published online July 20, 2023. doi:10.1007/s12031-023-02139-6