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Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients
The variants of electron transfer flavoprotein (ETFA, ETFB) and ETF dehydrogenase (ETFDH) are the leading cause of glutaric aciduria type II (GA-II). In this study, we identified 13 patients harboring six variants of two genes associated with GA-II. Out of the six variants, four were missense, and t...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466204/ https://www.ncbi.nlm.nih.gov/pubmed/34573316 http://dx.doi.org/10.3390/genes12091334 |
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author | Ali, Amanat Almesmari, Fatmah Saeed Ali Dhahouri, Nahid Al Saleh Ali, Arwa Mohammad Aldhanhani, Mohammed Ahmed Ali Mohamed Ahmed Vijayan, Ranjit Al Tenaiji, Amal Al Shamsi, Aisha Hertecant, Jozef Al Jasmi, Fatma |
author_facet | Ali, Amanat Almesmari, Fatmah Saeed Ali Dhahouri, Nahid Al Saleh Ali, Arwa Mohammad Aldhanhani, Mohammed Ahmed Ali Mohamed Ahmed Vijayan, Ranjit Al Tenaiji, Amal Al Shamsi, Aisha Hertecant, Jozef Al Jasmi, Fatma |
author_sort | Ali, Amanat |
collection | PubMed |
description | The variants of electron transfer flavoprotein (ETFA, ETFB) and ETF dehydrogenase (ETFDH) are the leading cause of glutaric aciduria type II (GA-II). In this study, we identified 13 patients harboring six variants of two genes associated with GA-II. Out of the six variants, four were missense, and two were frameshift mutations. A missense variant (ETFDH:p.Gln269His) was observed in a homozygous state in nine patients. Among nine patients, three had experienced metabolic crises with recurrent vomiting, abdominal pain, and nausea. In one patient with persistent metabolic acidosis, hypoglycemia, and a high anion gap, the ETFDH:p.Gly472Arg, and ETFB:p.Pro94Thrfs*8 variants were identified in a homozygous, and heterozygous state, respectively. A missense variant ETFDH:p.Ser442Leu was detected in a homozygous state in one patient with metabolic acidosis, hypoglycemia, hyperammonemia and liver dysfunction. The ETFDH:p.Arg41Leu, and ETFB:p.Ile346Phefs*19 variants were observed in a homozygous state in one patient each. Both these variants have not been reported so far. In silico approaches were used to evaluate the pathogenicity and structural changes linked with these six variants. Overall, the results indicate the importance of a newborn screening program and genetic investigations for patients with GA-II. Moreover, careful interpretation and correlation of variants of uncertain significance with clinical and biochemical findings are needed to confirm the pathogenicity of such variants. |
format | Online Article Text |
id | pubmed-8466204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84662042021-09-27 Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients Ali, Amanat Almesmari, Fatmah Saeed Ali Dhahouri, Nahid Al Saleh Ali, Arwa Mohammad Aldhanhani, Mohammed Ahmed Ali Mohamed Ahmed Vijayan, Ranjit Al Tenaiji, Amal Al Shamsi, Aisha Hertecant, Jozef Al Jasmi, Fatma Genes (Basel) Article The variants of electron transfer flavoprotein (ETFA, ETFB) and ETF dehydrogenase (ETFDH) are the leading cause of glutaric aciduria type II (GA-II). In this study, we identified 13 patients harboring six variants of two genes associated with GA-II. Out of the six variants, four were missense, and two were frameshift mutations. A missense variant (ETFDH:p.Gln269His) was observed in a homozygous state in nine patients. Among nine patients, three had experienced metabolic crises with recurrent vomiting, abdominal pain, and nausea. In one patient with persistent metabolic acidosis, hypoglycemia, and a high anion gap, the ETFDH:p.Gly472Arg, and ETFB:p.Pro94Thrfs*8 variants were identified in a homozygous, and heterozygous state, respectively. A missense variant ETFDH:p.Ser442Leu was detected in a homozygous state in one patient with metabolic acidosis, hypoglycemia, hyperammonemia and liver dysfunction. The ETFDH:p.Arg41Leu, and ETFB:p.Ile346Phefs*19 variants were observed in a homozygous state in one patient each. Both these variants have not been reported so far. In silico approaches were used to evaluate the pathogenicity and structural changes linked with these six variants. Overall, the results indicate the importance of a newborn screening program and genetic investigations for patients with GA-II. Moreover, careful interpretation and correlation of variants of uncertain significance with clinical and biochemical findings are needed to confirm the pathogenicity of such variants. MDPI 2021-08-27 /pmc/articles/PMC8466204/ /pubmed/34573316 http://dx.doi.org/10.3390/genes12091334 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ali, Amanat Almesmari, Fatmah Saeed Ali Dhahouri, Nahid Al Saleh Ali, Arwa Mohammad Aldhanhani, Mohammed Ahmed Ali Mohamed Ahmed Vijayan, Ranjit Al Tenaiji, Amal Al Shamsi, Aisha Hertecant, Jozef Al Jasmi, Fatma Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients |
title | Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients |
title_full | Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients |
title_fullStr | Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients |
title_full_unstemmed | Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients |
title_short | Clinical, Biochemical, and Genetic Heterogeneity in Glutaric Aciduria Type II Patients |
title_sort | clinical, biochemical, and genetic heterogeneity in glutaric aciduria type ii patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466204/ https://www.ncbi.nlm.nih.gov/pubmed/34573316 http://dx.doi.org/10.3390/genes12091334 |
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