Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction

Kedar Prabhakar S.; Dongerdiye Rashmi; Chilwirwar PoojaGupta VinodChiddarwar AshishDevendra RatiWarang PrashantPrasada HarshaSampagar AbhilashaBhat SunilChandrakala S.Madkaikar Manisha

首页> 外文期刊>Indian journal of pediatrics >Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction

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Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction

机译：Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction

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ObjectivesGlucose-6-phosphate isomerase (GPI) deficiency is an autosomal recessive genetic disorder causing hereditary non-spherocytic hemolytic anemia (HNSHA) coupled with a neurological disorder. The aim of this study was to identify GPI genetic defects in a cohort of Indian patients with HNSHA coupled with neurological dysfunction.MethodsThirty-five patients were screened for GPI deficiency in the HNSHA patient group; some were having neurological dysfunction. Enzyme activity was measured by spectrophotometric method. The genetic study was done by single-stranded conformation polymorphism (SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis by the restriction enzyme AciI for p.Arg347His (p.R347H) and confirmation by Sanger's sequencing.ResultsOut of 35 patients, 15 showed 35 to 70 loss of GPI activity, leading to neurological problems with HNSHA. Genetic analysis of PCR products of exon 12 of the GPI gene showed altered mobility on SSCP gel. Sanger's sequencing revealed a homozygous c1040G>A mutation predicting a p.Arg347His replacement which abolishes AciI restriction site. The molecular modeling analysis suggests p.Arg347 is involved in dimerization of the enzyme. Also, this mutation generates a more labile enzyme which alters its three-dimensional structure and function.ConclusionsThis report describes the high prevalence of p.Arg347His pathogenic variant identified in Indian GPI deficient patients with hemolytic anemia and neuromuscular impairment. It suggests that neuromuscular impairment with hemolytic anemia cases could be investigated for p.Arg347His pathogenic variant causing GPI deficiency because of neuroleukin activity present in the GPI monomer which has neuroleukin action at the same active site and generates neuromuscular problems as well as hemolytic anemia.

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《Indian journal of pediatrics》 |2019年第8期|692-699|共8页
作者
Kedar Prabhakar S.; Dongerdiye Rashmi; Chilwirwar PoojaGupta VinodChiddarwar AshishDevendra RatiWarang PrashantPrasada HarshaSampagar AbhilashaBhat SunilChandrakala S.Madkaikar Manisha;
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Mazumdar Shaw Canc Ctr, Dept Hematol Oncol & Bone Marrow Transplantat, Bangalore, Karnataka, India;

King Edward Mem Hosp, Dept Hematol, Mumbai, Maharashtra, India;

ICMR Natl Inst Immunohematol, Dept Hematogenet, King Edward Mem Hosp Campus, Mumbai 400012Manipal Univ, Kasturba Med Coll Hosp, Dept Pediat, Mangalore, IndiaKLES Dr Prabhakar Kore Hosp, Dept Pediat, Belagavi, India;

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正文语种英语
中图分类儿科学;
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Glucose-6-phosphate isomerase (GPI) deficiency; Neurological dysfunction; Hereditary non-spherocytic hemolytic anemia (HNSHA); Glycolysis; Molecular modeling; India;

Glucose Phosphate Isomerase Deficiency: High Prevalence of p.Arg347His Mutation in Indian Population Associated with Severe Hereditary Non-Spherocytic Hemolytic Anemia Coupled with Neurological Dysfunction

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