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Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan

Glycogen storage disease type I (GSD I) is a rare autosomal recessive inborn error of carbohydrate metabolism caused by the defects of glucose-6-phosphatase complex (G6PC). Disease causing variants in the G6PC gene, located on chromosome 17q21 result in glycogen storage disease type Ia (GSD Ia). Age...

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Autores principales: Gul, Bushra, Firasat, Sabika, Shan, Tayyaba, Tehreem, Raeesa, Afshan, Kiran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688888/
https://www.ncbi.nlm.nih.gov/pubmed/38033126
http://dx.doi.org/10.1371/journal.pone.0288965
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author Gul, Bushra
Firasat, Sabika
Shan, Tayyaba
Tehreem, Raeesa
Afshan, Kiran
author_facet Gul, Bushra
Firasat, Sabika
Shan, Tayyaba
Tehreem, Raeesa
Afshan, Kiran
author_sort Gul, Bushra
collection PubMed
description Glycogen storage disease type I (GSD I) is a rare autosomal recessive inborn error of carbohydrate metabolism caused by the defects of glucose-6-phosphatase complex (G6PC). Disease causing variants in the G6PC gene, located on chromosome 17q21 result in glycogen storage disease type Ia (GSD Ia). Age of onset of GSD Ia ranges from 0.5 to 25 years with presenting features including hemorrhage, hepatic, physical and blood related abnormalities. The overall goal of proposed study was clinical and genetic characterization of GSD Ia cases from Pakistani population. This study included forty GSD Ia cases presenting with heterogeneous clinical profile including hypoglycemia, hepatomegaly, lactic acidosis i.e., pH less than 7.2, hyperuricemia, seizures, epistaxis, hypertriglyceridemia (more than180 mg/dl) and sometimes short stature. All coding exons and intron-exon boundaries of G6PC gene were screened to identify pathogenic variant in 20 patients based on availability of DNA samples and willingness to participate in molecular analysis. Pathogenic variant analysis was done using PCR-Sanger sequencing method and pathogenic effect predictions for identified variants were carried out using PROVEAN, MutationTaster, Polyphen 2, HOPE, Varsome, CADD, DANN, SIFT and HSF software. Overall, 21 variants were detected including 8 novel disease causing variants i.e., G6PC (NM_000151.4):c.71A>C (p.Gln24Pro), c.109G>C(p.Ala37Pro), c.133G>C(p.Val45Leu), c.49_50insT c.205G>A(p.Asp69Asn), c.244C>A(p.Gln82Lys) c.322A>C(p.Thr108Pro) and c.322A>C(p.Cys284Tyr) in the screened regions of G6PC gene. Out of 13 identified polymorphisms, 3 were identified in heterozygous condition while 10 were found in homozygous condition. This study revealed clinical presentation of GSD Ia cases from Pakistan and identification of novel disease-causing sequence variants in coding region and intron-exon boundaries of G6PC gene.
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spelling pubmed-106888882023-12-01 Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan Gul, Bushra Firasat, Sabika Shan, Tayyaba Tehreem, Raeesa Afshan, Kiran PLoS One Research Article Glycogen storage disease type I (GSD I) is a rare autosomal recessive inborn error of carbohydrate metabolism caused by the defects of glucose-6-phosphatase complex (G6PC). Disease causing variants in the G6PC gene, located on chromosome 17q21 result in glycogen storage disease type Ia (GSD Ia). Age of onset of GSD Ia ranges from 0.5 to 25 years with presenting features including hemorrhage, hepatic, physical and blood related abnormalities. The overall goal of proposed study was clinical and genetic characterization of GSD Ia cases from Pakistani population. This study included forty GSD Ia cases presenting with heterogeneous clinical profile including hypoglycemia, hepatomegaly, lactic acidosis i.e., pH less than 7.2, hyperuricemia, seizures, epistaxis, hypertriglyceridemia (more than180 mg/dl) and sometimes short stature. All coding exons and intron-exon boundaries of G6PC gene were screened to identify pathogenic variant in 20 patients based on availability of DNA samples and willingness to participate in molecular analysis. Pathogenic variant analysis was done using PCR-Sanger sequencing method and pathogenic effect predictions for identified variants were carried out using PROVEAN, MutationTaster, Polyphen 2, HOPE, Varsome, CADD, DANN, SIFT and HSF software. Overall, 21 variants were detected including 8 novel disease causing variants i.e., G6PC (NM_000151.4):c.71A>C (p.Gln24Pro), c.109G>C(p.Ala37Pro), c.133G>C(p.Val45Leu), c.49_50insT c.205G>A(p.Asp69Asn), c.244C>A(p.Gln82Lys) c.322A>C(p.Thr108Pro) and c.322A>C(p.Cys284Tyr) in the screened regions of G6PC gene. Out of 13 identified polymorphisms, 3 were identified in heterozygous condition while 10 were found in homozygous condition. This study revealed clinical presentation of GSD Ia cases from Pakistan and identification of novel disease-causing sequence variants in coding region and intron-exon boundaries of G6PC gene. Public Library of Science 2023-11-30 /pmc/articles/PMC10688888/ /pubmed/38033126 http://dx.doi.org/10.1371/journal.pone.0288965 Text en © 2023 Gul et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Gul, Bushra
Firasat, Sabika
Shan, Tayyaba
Tehreem, Raeesa
Afshan, Kiran
Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan
title Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan
title_full Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan
title_fullStr Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan
title_full_unstemmed Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan
title_short Mutational analysis and clinical investigations of medically diagnosed GSD 1a patients from Pakistan
title_sort mutational analysis and clinical investigations of medically diagnosed gsd 1a patients from pakistan
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688888/
https://www.ncbi.nlm.nih.gov/pubmed/38033126
http://dx.doi.org/10.1371/journal.pone.0288965
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