Novel mutation in SMPD1 gene found by whole-exome sequencing in Niemann-Pick disease patient

Abstract

Niemann-Pick diseases (NPD) are heterogeneous and autosomal recessive disorders and are classified into four types: type A, type B, type C1, and type C2 that type A and B Niemann–Pick is induced via SMPD1 gene mutations. Accumulation of sphingomyelin in the central nervous system is the first and prominent cause of the classical infantile type (type A) of NPD which is the most extreme form of NPD and causes severe central nervous system decay, hepatosplenomegaly, and fatal disorder. Our aim with this study was to propose that the novel likely pathogenic variant, c.1586G>C (p.529Trp>Ser) can cause Niemann-Pick disease type A. Present study involves a 2 years-old child as a result of a consanguineous marriage that has been diagnosed with clumsiness and gait disturbance at the beginning, and include hypotonia, microcephaly, severe hepatosplenomegaly in infancy, speech and developmental delay, dysphagia during the disease course. Considering the symptoms of Niemann-Pick disease, the patient's DNA was extracted and used for molecular studying and sequencing. Performing WES on proband identified a novel likely pathogenic, c.1586G>C (p.529Trp>Ser) mutation of the SMPD1 gene. This gene has an autosomal recessive inheritance pattern. To date, c.1586G>C (p.529Trp>Ser) likely pathogenic variant has not been observed or reported in the world. This mutation locates in the 6415659 positions and disrupts the function of the SMPD1 gene, causing symptoms of Niemann-Pick disease type A. The mutation reported in this article is associated with the NPD type A, disease phenotype, molecular findings and clinical observations underscore it.