Mutational spectrum of SMPD1 gene in Pakistani Niemann-Pick disease patients

Cheema, Huma Arshad; Rasool, Iqra Ghulam; Anjum, Muhammad Nadeem; Zahoor, Muhammad

doi:10.12669/pjms.36.3.467

Cited by 10 publications

(4 citation statements)

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“…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 Reduced acid sphingomyelinase activity in fibroblasts, Lymphoblasts or in peripheral white blood cells [ 28 ] MPS KPK, Punjab, Baluchistan, FATA 8 families Not mentioned Not mentioned DNA extraction Sanger sequencing Insilico (QAU) Linkage analysis followed by sequence analysis of the gene detected four novel (p.Phe216Ser, p.Met38Arg, p.Ala291Ser, p.Glu121Argfs*37) and two reported (p.Pro420Arg, p.Arg386Cys) mutations in the eight families. In silico structural and functional analysis predicted that these mutations disrupt the function of GALNS protein through fluctuating its three-dimensional structure, stability, and binding affinity and produce severe phenotypes Not mentioned [ 29 ] MPS Pakistan Thirteen MPS1-affected children from 12 unrelated cohorts were enrolled Not mentioned Not mentioned Results Six IDUA gene mutations were mapped co-segregating with the recessive pattern of inheritance including a novel variant.…”

Section: Methodsmentioning

confidence: 99%

“…Through tandem-MS technology we can simultaneously test for more than 40 disorders. Conventional methods help us to diagnose common disorders like CH, congenital adrenal [12][13][14][15][16][17]. But for a proportion of IEM, the causal gene or the mutations in various genes remain to be identified in our ethnic population and thus newborn screening (NBS) program encompasses a strong research component as well [5].…”

Section: Discusssionmentioning

confidence: 99%

“…These disorders have been tested at a number of centers, and samples mostly collected from intensive care departments, pediatric units and from hematology units of tertiary care hospitals in Pakistan including Karachi, Lahore, Islamabad, Peshawar and Faisalabad. Mostly patients referred to these centers for diagnosis and better management [5,[12][13][14][15] (Tables 1, 2). It is apparent from the data compiled and presented that there is a need for establishing/identifying reliable labs for biochemical testing and genetic confirmation and taken together, warrant formulation of a standard protocol for testing and follow up of IEM positive cases in the country.…”

Section: Discusssionmentioning

confidence: 99%

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Trends of congenital hypothyroidism and inborn errors of metabolism in Pakistan

Mansoor

2020

Orphanet J Rare Dis

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Background Metabolic disorders are heterogeneous group of genetic disorders that are responsible for significant neonatal and infant morbidity and mortality worldwide. In developing countries like Pakistan where infant mortality is high current population based studies are unable to gauge contribution of metabolic disorders in causing mortality and morbidity. It is essential to address this gap by a review of available scattered Pakistani data related to metabolic disorders specifically congenital hypothyroidism and inborn error of metabolism to calculate probable burden of these disorders. Main body Unfortunately currently in Pakistan newborn screening which identifies these illnesses at birth as a preventive strategy are not available. For current review data was collected through a systematic search of published articles (including data related to screening in certain subgroups of patients admitted to pediatric/neonatal intensive care units, patients with developmental delay/mental retardation). Conclusion The primary aim of this review was to get an estimate of the disease burden in the Pakistani population as true prevalence of Congenital Hypothyroidism and Inborn Errors of Metabolism in Pakistan is not available. This systematic review will help us to identify the rough idea about the scale of problem in Pakistan.

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Section: Methodsmentioning

confidence: 99%

Section: Discusssionmentioning

confidence: 99%

Section: Discusssionmentioning

confidence: 99%

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Trends of congenital hypothyroidism and inborn errors of metabolism in Pakistan

Mansoor

2020

Orphanet J Rare Dis

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“…In Pakistan, despite consanguineous marriages being relatively common in this country, even less has been reported on this rare disease, with the first genetic demographic study having been completed in March 2019 by Huma Arshad Cheema and her colleagues in Lahore [ 7 ]. Although our team was unable to find a comprehensive study of autosomal recessive disorders in Pakistan, one study has concluded that a higher rate of morbidity and mortality exists in the UK among Pakistani children due to autosomal recessive conditions with association to the custom of consanguineous marriages [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Niemann-Pick Disease on Bone Marrow Trephine: A Rare Manifestation

Qadir¹,

Baig²,

Adil³

et al. 2021

Cureus

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Niemann-Pick disease has an autosomal recessive inheritance pattern and occurs due to a deficiency of a lysosomal enzyme, sphingomyelinase. It causes variable clinical signs and symptoms such as hepatosplenomegaly, delayed milestones, and peripheral cytopenia due to bone marrow involvement. Here, we report a case of a child who presented with hepatosplenomegaly and pancytopenia, who was later found to have Niemann-Pick disease on bone marrow examination. This case highlights the case presentations of this rare disease and the importance of bone marrow trephine in prompt diagnosis and management of a patient.

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SMPD1 gene variants in patients with β-Thalassemia major

Dursun

Özen

2023

Mol Biol Rep

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Background β-thalassemia major and Niemann-Pick diseases have similar clinical and laboratory findings. We aimed to investigate the effects of sphingomyelin phosphodiesterase 1 (SMPD1) gene variants on the clinical and laboratory findings in patients with β-thalassemia major. Methods and results This study included 45 patients who were followed up for β-thalassemia major in our clinic. Plasma chitotriosidase, leukocyte acid sphingomyelinase, liver enzymes, ferritin, hemogram, biochemical parameters, SMPD1 gene variant analysis, cardiac T2* MRI, and liver R2 MRI were assessed in all patients. The SMPD1 gene c.132_143del, p.A46_L49del (c.108GCTGGC[4] (p.38AL[4])) (rs3838786) variant was detected in 9 of 45 (20.0%) patients. Plasma chitotriosidase, ferritin, acetyl aminotransferase, and alanine aminotransferase levels were significantly higher in patients with the gene variant than in those without (p < 0.05). Leukocyte acid sphingomyelinase levels were significantly lower in patients with the gene variant than in those without (p < 0.05). Conclusion These results imply that the clinical and laboratory findings and some features of disease progression in patients with β-thalassemia major are similar to those of Niemann-Pick disease. They also suggest that SMPD1 gene c.132_143del, p.A46_L49del (c.108GCTGGC[4] (p.38AL[4])) (rs3838786) variant may underlie these clinical findings in patients with β-thalassemia major.

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Mutational spectrum of SMPD1 gene in Pakistani Niemann-Pick disease patients

Cited by 10 publications

References 24 publications

Trends of congenital hypothyroidism and inborn errors of metabolism in Pakistan

Trends of congenital hypothyroidism and inborn errors of metabolism in Pakistan

Niemann-Pick Disease on Bone Marrow Trephine: A Rare Manifestation

SMPD1 gene variants in patients with β-Thalassemia major

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