A 2-bp deletion mutation in SMPD1 gene leading to lysosomal acid sphingomyelinase deficiency in a Chinese consanguineous pedigree
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Han Kang
Abstract
Objectives
Niemann–Pick disease type A (NPDA, MIM: 257200) is an autosomal recessive sphingolipidosis caused by lysosomal acid sphingomyelinase (ASM) deficiency. A cluster of genes located at chromosome 11p15 have been reported to be imprinted genes, such as TSSC5, TSSC3, and ZNF215 that flanking SMPD1 gene. It was reported by a few recent studies that SMPD1 gene was paternally imprinted and maternally preferentially expressed.
Case presentation
A five-month-old boy with severe anemia, hepatosplenomegly and bone marrow foam cells was recruited from a complete cousin couple. To determine whether boy suffered from NPDA, ASM activity and SMPD1 gene sequencing were performed on available individuals of this pedigree including the proband, his parents and sister. The ASM activities of proband and parents showed deficiency (17.7 nmol/h/g-protein) and about 50% decreased (83.3 nmol/h/g-protein), respectively, compared with normal controls (204.5 nmol/h/g-protein). SMPD1 gene sequencing in the proband revealed a homozygous mutation c.1420_1421del, which leads to an open reading frameshift and a premature stop codon. The parents and some individuals of this family demonstrated heterozygous mutation at this locus. To investigate whether SMPD1 gene is imprinted as reported previously, the expression of RNA level was studied in the whole family members available. The members with heterozygous mutation for c.1420_1421del showed that both paternal and maternal inherited alleles were expressed.
Conclusions
This study reported a c.1420_1421del mutation in SMPD1 gene which caused ASM activity decrease and this locus was biallelically expressed in heterozygous subjects implicating SMPD1 is not imprinted in this family.
Funding source: Ethics Committee of Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China
Acknowledgments
This study was performed in Prenatal diagnosis department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, UESTC, No 1617 Riyue Road, Chengdu, Sichuan Province, China, 610000.
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Research funding: None declared.
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Author contribution: Kangmo Lu, Han Kang contributed to study design and manuscript drafting and revision. Min Zhou, Han Kang and Chengxiu Xie assisted with clinical diagnosis and auxiliary examination. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: Research involving human subjects has been approved by the Ethics Committee of Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China.
References
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- From pregnancy to breastfeeding: adequate maternal body mass index is essential to prevent a high body mass index in your children
- Screening of non-syndromic early-onset child and adolescent obese patients in terms of LEP, LEPR, MC4R and POMC gene variants by next-generation sequencing
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- A 2-bp deletion mutation in SMPD1 gene leading to lysosomal acid sphingomyelinase deficiency in a Chinese consanguineous pedigree
