Identifying the Type of Niemann Pick Disease through Next Generation Sequencing Technology

Abstract

Niemann Pick Type A Disease is an autosomal recessive disorder which is caused by mutations in SMPD1 gene encoding ASM protein. The gene is responsible for hydrolysis of Sphingomyelin into Ceramide within lysosomes. SMPD1 is located on chromosome 11 in a region between p15.1 p15.4. The type A NPD is a severe illness, characterized by neurovisceral symptoms, mainly hepatosplenomegaly, poor growth, cherry red spot and respiratory failure and a short life span. In this study, a Pakistani family was recruited from PIMS Hospital, Islamabad with symptoms supportive of NPD. The main objective of this study was to analyze the responsible variant through whole exome sequencing. Molecular diagnosis was utilized to filter the specific variant resulting in clinical manifestation of NPD. The specific variant for the disorder shows autosomal recessive inheritance pattern and proband shows missense mutation in exon 1 which is likely the cause of NPD in the family. The results will provide insight into further analysis and characterization of NPD and its related diseases. Protein expression studies are required to illustrate the effect of variant on protein stability, structure, function, and its role in development of phenotypic characteristics.