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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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