Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy

Nor A zimah Abdul Azize, Wan Z urinah Wan Ngah, Zulhabri Othman, Norsiah Md Desa, Chen B ee Chin, Zabedah Md Yunus, Anand Mohan, Teh S iao Hean, Syed Zulkifli Syed Zakaria, Ngu Lock-Hock

Research output: Contribution to journalArticle

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Abstract

Glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death. We screened 14 patients from 13 families with clinical and biochemical features suggestive of GCE for mutation in AMT, GLDC and GCSH genes by direct sequencing and genomic rearrangement of GLDC gene using a multiplex ligation-dependant probe amplification. We identified mutations in all 14 patients. Seven patients (50%) have biallelic mutations in GLDC gene, six patients (43%) have biallelic mutations in AMT gene and one patient (7%) has mutation identified in only one allele in GLDC gene. Majority of the mutations in GLDC and AMT were missense mutations and family specific. Interestingly, two mutations p.Arg265His in AMT gene and p.His651Arg in GLDC gene occurred in the Penan sub-population. No mutation was found in GCSH gene. We concluded that mutations in both GLDC and AMT genes are the main cause of GCE in Malaysian population.

Original languageEnglish
Pages (from-to)593-597
Number of pages5
JournalJournal of Human Genetics
Volume59
Issue number11
DOIs
Publication statusPublished - 1 Nov 2014

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Glycine Decarboxylase Complex H-Protein
Aminomethyltransferase
Glycine Dehydrogenase (Decarboxylating)
Nonketotic Hyperglycinemia
Mutation
Genes
Glycine
Inborn Errors Metabolism
Muscle Hypotonia
Brain Diseases
Apnea
Missense Mutation
Population

ASJC Scopus subject areas

  • Medicine(all)

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Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy. / Azize, Nor A zimah Abdul; Ngah, Wan Z urinah Wan; Othman, Zulhabri; Md Desa, Norsiah; Chin, Chen B ee; Md Yunus, Zabedah; Mohan, Anand; Hean, Teh S iao; Syed Zakaria, Syed Zulkifli; Lock-Hock, Ngu.

In: Journal of Human Genetics, Vol. 59, No. 11, 01.11.2014, p. 593-597.

Research output: Contribution to journalArticle

Azize, Nor A zimah Abdul ; Ngah, Wan Z urinah Wan ; Othman, Zulhabri ; Md Desa, Norsiah ; Chin, Chen B ee ; Md Yunus, Zabedah ; Mohan, Anand ; Hean, Teh S iao ; Syed Zakaria, Syed Zulkifli ; Lock-Hock, Ngu. / Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy. In: Journal of Human Genetics. 2014 ; Vol. 59, No. 11. pp. 593-597.
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AU - Md Desa, Norsiah

AU - Chin, Chen B ee

AU - Md Yunus, Zabedah

AU - Mohan, Anand

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AB - Glycine encephalopathy (GCE) or nonketotic hyperglycinemia is an inborn error of glycine metabolism, inherited in an autosomal recessive manner due to a defect in any one of the four enzymes aminomethyltransferase (AMT), glycine decarboxylase (GLDC), glycine cleavage system protein-H (GCSH) and dehydrolipoamide dehydrogenase in the glycine cleavage system. This defect leads to glycine accumulation in body tissues, including the brain, and causes various neurological symptoms such as encephalopathy, hypotonia, apnea, intractable seizures and possible death. We screened 14 patients from 13 families with clinical and biochemical features suggestive of GCE for mutation in AMT, GLDC and GCSH genes by direct sequencing and genomic rearrangement of GLDC gene using a multiplex ligation-dependant probe amplification. We identified mutations in all 14 patients. Seven patients (50%) have biallelic mutations in GLDC gene, six patients (43%) have biallelic mutations in AMT gene and one patient (7%) has mutation identified in only one allele in GLDC gene. Majority of the mutations in GLDC and AMT were missense mutations and family specific. Interestingly, two mutations p.Arg265His in AMT gene and p.His651Arg in GLDC gene occurred in the Penan sub-population. No mutation was found in GCSH gene. We concluded that mutations in both GLDC and AMT genes are the main cause of GCE in Malaysian population.

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