Mahmoud M Sirdah1,2, Mohammad E Shubair3, Mustafa S Al-Kahlout4, Jamal M Al-Tayeb4, Josef T Prchal2,5, N Scott Reading2,5. 1. a Biology Department , Al Azhar University-Gaza , Gaza , Palestine. 2. b Division of Hematology, Department of Internal Medicine , School of Medicine, University of Utah , Salt Lake City , UT , USA. 3. c Department of Medical Laboratory Sciences , Islamic University-Gaza , Gaza , Palestine. 4. d Palestinian Ministry of Health , Al Nasser Pediatric Hospital , Palestine. 5. e Institute for Clinical and Experimental Pathology, ARUP Laboratories , Salt Lake City , UT , USA.
Abstract
BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. OBJECTIVES: Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. METHODS: Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. RESULTS: In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficient children, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). CONCLUSION: We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.
BACKGROUND:Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked inherited enzymopathic disorder affecting more than 500 million people worldwide. It has so far been linked to 217 distinct genetic variants in the exons and exon-intron boundaries of the G6PD gene, giving rise to a wide range of biochemical heterogeneity and clinical manifestations. OBJECTIVES: Reports from different settings suggested the association of intronic and other mutations outside the reading frame of the G6PD gene with reduced enzyme activity and presenting clinical symptoms. The present study aimed to investigate any association of other variations apart of the exonic or exonic intronic boundaries in the development of G6PD deficiency. METHODS: Sixty-seven unrelated Palestinian children admitted to the pediatric hospital with hemolytic crises due to G6PD deficiency were studied. RESULTS: In our Palestinian cohort of 67 [59 males (M) and 8 females (F)] G6PD-deficientchildren, previously hospitalized for acute hemolytic anemia due to favism, molecular sequencing of the G6PD gene revealed four cases (3M and 1F) that did not have any of the variants known to cause G6PD deficiency, but the 3' UTR c.*+357A>G (rs1050757) polymorphism in association with IVS 11 (c.1365-13T>C; rs2071429), and c.1311C>T (rs2230037). CONCLUSION: We now provide an additional evidence form Palestinian G6PD-deficient subjects for a possible role of 3' UTR c.*+357 A>G, c.1365-13T>C, and/or c.1311C>T polymorphism for G6PD deficiency, suggesting that not only a single variation in the exonic or exonic intronic boundaries, but also a haplotype of G6PD should considered as a cause for G6PD deficiency.
Authors: Richard O Francis; Angelo D'Alessandro; Andrew Eisenberger; Mark Soffing; Randy Yeh; Esther Coronel; Arif Sheikh; Francesca Rapido; Francesca La Carpia; Julie A Reisz; Sarah Gehrke; Travis Nemkov; Tiffany Thomas; Joseph Schwartz; Chaitanya Divgi; Debra Kessler; Beth H Shaz; Yelena Ginzburg; James C Zimring; Steven L Spitalnik; Eldad A Hod Journal: J Clin Invest Date: 2020-05-01 Impact factor: 14.808
Authors: Dewi A Wisnumurti; Yunia Sribudiani; Robert M Porsch; Ani M Maskoen; Sri E Rahayuningsih; Eni K Asni; Frank Sleutels; Wilfred F J van Ijcken; Abdurachman Sukadi; Tri H Achmad Journal: BMC Pediatr Date: 2019-12-20 Impact factor: 2.125