Abstract
Objective:Genetic variation analysis of rare autosomal recessive Niemann-Pick disease (NPD) Pakistani patients.Methods:We sequenced the SMPD1 gene including its all coding and flanking regions in seven unrelated sporadic patients suffering from Niemann-Pick disease through targeted exome sequencing. Genetic variants mapping and their protein predictions were evaluated using different bioinformatics tools and clinical phenotypes were correlated. The study was conducted from January 2018 to March 2019 at The Children’s Hospital Lahore.Results:We have mapped five different mutations in SMPD1 gene of enrolled patients with a novel homozygous missense variant (c.1718G>C) (p.Trp573Ser) in one patient. A missense mutation (c.1267C>T) (p.His423Tyr) has been identified in three unrelated patients. A nonsense mutation (c.1327C>T) (p.Arg443Term) and one missense mutation (c.1493G>A) (p.Arg498His) mapped in one patient each. A compound heterozygous mutation has been mapped in one patient (c.740G>A) (p.Gly247Asp); (c.1493G>A) (p.Arg498His). Pathogenic effect of novel variant has been predicted through in-silico analysis and has not been reported in general overall population in the globe.Conclusion:This is the first report of genetic demographic assessment of Niemann-Pick disease in Pakistan. The mapped mutations would be helpful to build a disease variants algorithm of Pakistani population. This will be used for determining disease clinical magnitude along with provision of genetic screening services in affected families.
Highlights
Niemann-Pick disease (NPD) OMIM # 607608; is caused by the deficiency or inactivity of acid sphingomyelinase enzyme (ASM) EC 3.1.4.12, encoded by SMPD1 gene
NPD type A affects in early infancy with organomegaly and a neurodegenerative course manifested around three months of age leading to demise by three years while, with NPD type B patients often survive into adulthood correlate with hepatosplenomegaly and respiratory complications and have less or no CNS involvement.[4,5]
We have identified five different disease causing mutations of SMPD1 gene in Niemann-Pick disease unrelated patients from consanguineous families
Summary
Niemann-Pick disease (NPD) OMIM # 607608; is caused by the deficiency or inactivity of acid sphingomyelinase enzyme (ASM) EC 3.1.4.12, encoded by SMPD1 gene. The disease is associated with mutations in ASM encoding gene SMPD1, resulting in sphingomyelin accumulation in reticuloendothelial cells and hepatocytes.[1] Clinically, NPD patients usually present with enlargement of body organs such as liver and spleen (hepatosplenomegaly), fail to weight gaining and growth in a usual way (failure to thrive), progressive loss of mental abilities, loss of muscle movement, eye abnormality called a cherryred spot and recurrent lung infections. Pak J Med Sci March - April 2020 Vol 36 No 3 www.pjms.org.pk 479 be classified into two common types: NPD type A and NPD type B, based on the onset of the disease, severity of symptoms and type of organs affected both caused by variation in SMPD1 gene. The NPD types A and B has been reported for affecting 1 in 250,000 individuals.[2,3] NPD type A affects in early infancy with organomegaly and a neurodegenerative course manifested around three months of age leading to demise by three years while, with NPD type B patients often survive into adulthood correlate with hepatosplenomegaly and respiratory complications and have less or no CNS involvement.[4,5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
