Deep sequencing of SMPD1 gene revealed a heterozygous frameshift mutation (p.Ser192Alafs) in a Palestinian infant with Niemann-Pick disease type A: A case report

被引：4
作者：
Nasereddin A. [1 ,2 ]
Ereqat S. [3 ]
机构：
[1] Al-Quds Nutrition and Health Research Institute, Faculty of Medicine, Al-Quds University, P.O. Box 20760, Abu-Dis-Esat Jerusalem
[2] Genomics Applications Lab, Core Research Facility, Faculty of Medicine, Hebrew University, Jerusalem
[3] Biochemistry and Molecular Biology Department, Faculty of Medicine, Al-Quds University, Abu Dis-East Jerusalem
来源：
Journal of Medical Case Reports | / 12卷 / 1期
关键词：
Mutation; Niemann-Pick disease type A; Palestinian child; Sphingomyelinase deficiency;
D O I：
10.1186/s13256-018-1805-x
中图分类号：
学科分类号：
摘要：
Background: Niemann-Pick disease is caused by reduced level of the lysosomal enzyme acid sphingomyelinase. Children can survive between 2 and 12 years based on the disease type. Two main types are well known: type A and B. Niemann-Pick disease type A is characterized by severe central nervous system deterioration and hepatosplenomegaly while type B is a progressive hypersplenism accompanied with gradual deterioration of pulmonary function. Case presentation: We describe an 11-month-old Palestinian baby boy with hepatosplenomegaly, hypotonia, delayed motor development, laryngomalacia, bilateral cherry-red spots, and failure to thrive. Metabolic screening, blood count, differential tests, immunology screen, infectious disease screen, urine, biochemical tests as well as molecular diagnosis were performed. The molecular diagnosis was done by amplifying the whole sphingomyelin phosphodiesterase 1 (SMPD1) gene, followed by deep sequencing. The obtained sequences were aligned, de novo assembled and compared to human reference gene (GenBank GeneID: NG-011780.1, Ensembl version ENSG00000166311 and protein identified as UniProtKB - P17405). Two known mutations were identified in our patient: the pathogenic frameshift mutation NM-000543.4(SMPD1):c.573delT (p.Ser192Alafs) and the benign polymorphism NM-000543.4(SMPD1):c.107T>C (p.Val36Ala). The enzyme study showed a very low level of enzymatic activity of acidic sphingomyelinase (0.1 nmol/ml per hour). Correlations between clinical findings, laboratory data, and sequence analysis are presented. Conclusions: In conclusion, this is the first report about a heterozygote frameshift p.Ser192AlafsX65 in a Palestinian patient with Niemann-Pick disease type A, emphasizing the importance of deep sequencing in genetic diagnosis of this rare inherited disease. © 2018 The Author(s).
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