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Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1

Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from in...

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Autores principales: Abdul Wahab, Siti Aishah, Yakob, Yusnita, Abdul Azize, Nor Azimah, Md Yunus, Zabedah, Huey Yin, Leong, Mohd Khalid, Mohd Khairul Nizam, Lock Hock, Ngu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031822/
https://www.ncbi.nlm.nih.gov/pubmed/27672653
http://dx.doi.org/10.1155/2016/4074365
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author Abdul Wahab, Siti Aishah
Yakob, Yusnita
Abdul Azize, Nor Azimah
Md Yunus, Zabedah
Huey Yin, Leong
Mohd Khalid, Mohd Khairul Nizam
Lock Hock, Ngu
author_facet Abdul Wahab, Siti Aishah
Yakob, Yusnita
Abdul Azize, Nor Azimah
Md Yunus, Zabedah
Huey Yin, Leong
Mohd Khalid, Mohd Khairul Nizam
Lock Hock, Ngu
author_sort Abdul Wahab, Siti Aishah
collection PubMed
description Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome.
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spelling pubmed-50318222016-09-26 Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1 Abdul Wahab, Siti Aishah Yakob, Yusnita Abdul Azize, Nor Azimah Md Yunus, Zabedah Huey Yin, Leong Mohd Khalid, Mohd Khairul Nizam Lock Hock, Ngu Biomed Res Int Research Article Glutaric aciduria type 1 (GA1) is an autosomal recessive metabolic disorder caused by deficiency of glutaryl-CoA dehydrogenase enzyme encoded by the GCDH gene. In this study, we presented the clinical and molecular findings of seven GA1 patients in Malaysia. All the patients were symptomatic from infancy and diagnosed clinically from large excretion of glutaric and 3-hydroxyglutaric acids. Bidirectional sequencing of the GCDH gene revealed ten mutations, three of which were novel (Gln76Pro, Glu131Val, and Gly390Trp). The spectrum of mutations included eight missense mutations, a nonsense mutation, and a splice site mutation. Two mutations (Gln76Pro and Arg386Gln) were homozygous in two patients with parental consanguinity. All mutations were predicted to be disease causing by MutationTaster2. In conclusion, this is the first report of both clinical and molecular aspects of GA1 in Malaysian patients. Despite the lack of genotype and phenotype correlation, early diagnosis and timely treatment remained the most important determinant of patient outcome. Hindawi Publishing Corporation 2016 2016-09-08 /pmc/articles/PMC5031822/ /pubmed/27672653 http://dx.doi.org/10.1155/2016/4074365 Text en Copyright © 2016 Siti Aishah Abdul Wahab et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Abdul Wahab, Siti Aishah
Yakob, Yusnita
Abdul Azize, Nor Azimah
Md Yunus, Zabedah
Huey Yin, Leong
Mohd Khalid, Mohd Khairul Nizam
Lock Hock, Ngu
Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
title Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
title_full Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
title_fullStr Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
title_full_unstemmed Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
title_short Clinical and Mutational Analysis of the GCDH Gene in Malaysian Patients with Glutaric Aciduria Type 1
title_sort clinical and mutational analysis of the gcdh gene in malaysian patients with glutaric aciduria type 1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5031822/
https://www.ncbi.nlm.nih.gov/pubmed/27672653
http://dx.doi.org/10.1155/2016/4074365
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