Investigating Mutations in Genes Involved in Lysosomal Storage Metabolic Diseases by Next-Generation Sequencing in Two Families in Khuzestan Province

Lysosomal storage diseases (LSDs) are a group of metabolic diseases that are caused by mutations in lysosomal enzymes and lead to the accumulation of lysosomal substrates. Gaucher's disease and Niemann-Pick are two autosomal recessive lysosomal disorders caused by mutations in the beta-glucosidase gene and sphingomyelin phosphodiesterase 1 gene, respectively. A powerful diagnostic tool based on Whole-Exome Sequencing (WES) technology paves the way for more appropriate genetic counseling by helping with faster diagnosis.

Whole-Exome sequencing was done using the WES method after sampling in a tube containing EDTA anticoagulant and DNA extraction in this research. After finding the candidate gene, in order to confirm the variant, the PCR method was used for amplification, and Chromas software was used for sequence reading.

The results of sequencing exon 8 of the GBA gene in the first family patient indicated the known homozygous mutation of Gaucher disease in the GBA gene: c.79C > T:p.I260S. The results of sequencing the exon 9 of the NPC1 gene in the patient of the second family indicate a homozygous mutation in the NPC1 gene: c.1350C>G.p.I450M, which is a new variant in Niemanpik patients.

The WES method can reduce the time to diagnose the pathogenic variants of lysosomal storage diseases (LSDs) by simultaneously evaluating several genes and helping to treat patients.