title: Mutation analysis of glycine decarboxylase, aminomethyltransferase and glycine cleavage system protein-H genes in 13 unrelated families with glycine encephalopathy.
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.
authors.affiliation: Molecular Diagnostics and Protein Unit, Specialised Diagnostics Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Nor Azimah Abdul
authors.initials: NA
authors.lastname: Azize
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur, Malaysia.
authors.forename: Wan Zurinah Wan
authors.initials: WZ
authors.lastname: Ngah
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur, Malaysia.
authors.forename: Zulhabri
authors.initials: Z
authors.lastname: Othman
authors.affiliation: Molecular Diagnostics and Protein Unit, Specialised Diagnostics Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Norsiah
authors.initials: N
authors.lastname: Md Desa
authors.affiliation: Genetic Department, Kuala Lumpur Hospital, Jalan Pahang, Kuala Lumpur, Malaysia.
authors.forename: Chen Bee
authors.initials: CB
authors.lastname: Chin
authors.affiliation: Biochemistry Unit, Specialised Diagnostics Centre, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Zabedah
authors.initials: Z
authors.lastname: Md Yunus
authors.affiliation: Department of Paediatrics, Hospital Bintulu, Sarawak, Malaysia.
authors.forename: Anand
authors.initials: A
authors.lastname: Mohan
authors.affiliation: Department of Paediatrics, Hospital Miri, Sarawak, Malaysia.
authors.forename: Teh Siao
authors.initials: TS
authors.lastname: Hean
authors.affiliation: UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Kuala Lumpur, Malaysia.
authors.forename: Syed Zulkifli
authors.initials: SZ
authors.lastname: Syed Zakaria
authors.affiliation: Genetic Department, Kuala Lumpur Hospital, Jalan Pahang, Kuala Lumpur, Malaysia.
authors.forename: Ngu
authors.initials: N
authors.lastname: Lock-Hock
mesh_terms: D050960:Aminomethyltransferase / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D050961:Glycine Decarboxylase Complex H-Protein / Q000235:genetics*; D050841:Glycine Dehydrogenase (Decarboxylating) / Q000235:genetics*; D006801:Humans; D020158:Hyperglycinemia, Nonketotic / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D009154:Mutation
chemical_list: D050961:Glycine Decarboxylase Complex H-Protein; D050841:Glycine Dehydrogenase (Decarboxylating); D050960:Aminomethyltransferase