A novel mutation in SMPD1 gene in a patient with Niemann-Pick disease

سال انتشار: 1395
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 848

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شناسه ملی سند علمی:

MPHBS01_159

تاریخ نمایه سازی: 22 آبان 1395

چکیده مقاله:

Mutations in the sphingomyelinphosphodiesterase 1 gene (SMPD1) located on chromosome 11 cause the deficient activity of lysosomal acid sphingomyelinase (ASM) protein and subsequently leads to the types A and B of Niemann-Pick disease (NPD) with the autosomal recessive inheritance. Types A or B of the disease were described based on the manifestation of the neurological symptoms. Here, we present a one year old male patient suspected to the Niemann-Pick disease with the symptoms of splenomegaly, hepatomegaly who referred to our center for the definitive diagnosis of the disease. A novel deletion mutation was detected by molecular testing in the SMPD1 gene. All the coding regions of SMPD1 gene were evaluated by direct sequencing; segregation analysis was performed for his consanguineous parents. A regulatory variant at (c.-230C>A), one missense variant (c.107T>C), and one deletion mutation (c.946-961del16) were identified in the patient. The patient was homozygous for the 16bp deletion mutation at the position c.946-961del16 which leads to frame shift stop codon (p.P316MfsX64). Segregation analysis of the variation among other related members of the family was positive for the pathogenicity of this variant. Mutation in SMPD1 shows phenotypic correlation and predicts the type of disease. In silico analysis with mutation taster tool predicted that this alternation might change the protein features and splice sites in subsequent intron, also this mutation could be responsible for pathogenic effects in this patient. Some investigations argued that, this type of Niemann-pick disease is difficult disorder to be clinically diagnosed; hence this study could demonstrate the fundamental role of genetic testing in definitive diagnosis. Sequencing is recommended for at risk family members to benefit from reoccurrence though treatment are in clinical trial and physicians could help affected and their family members for disease management.

نویسندگان

Sepideh Mikaeeli

Genetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

Bahareh Rabbani

Genetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

Reza Shervin Badv

Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Majid Maleki

Genetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran