title: Molecular genetic and potential biochemical characteristics of patients with T-protein deficiency as a cause of glycine encephalopathy (NKH).
abstract: A defect in the P-protein component of the glycine cleavage system has been the most frequent abnormality found in patients with glycine encephalopathy (NKH). In a retrospective study of a more specific group of NKH patients, however, we found that >50% had T-protein mutations. The patients studied had one or more of the following unusual biochemical findings: residual glycine cleavage system activity in liver assayed by the standard method or a newly developed micromethod, residual glycine cleavage system activity in lymphoblasts, and/or increased amniotic fluid glycine/serine ratio with a normal amniotic fluid glycine level in prenatal diagnosis. The selected patients had a much higher incidence of T-protein defects than expected in the general NKH patient population. We report, here, three novel mutations and five polymorphisms in the T-protein gene, PCR/restriction enzyme methods for one mutation (R296H) and two polymorphisms (E211K and R318R), and an estimation of their frequency in normal controls. The co-occurrence of the polymorphism E211K with the mutation R320H in patients with a severe phenotype is discussed.
authors.affiliation: Department of Pediatrics, University of British Columbia, and Biochemical Genetics Laboratory, B.C.'s Children's Hospital, Vancouver, BC, Canada.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Toone
authors.forename: Derek A
authors.initials: DA
authors.lastname: Applegarth
authors.forename: Harvey L
authors.initials: HL
authors.lastname: Levy
authors.forename: Marion B
authors.initials: MB
authors.lastname: Coulter-Mackie
authors.forename: Gary
authors.initials: G
authors.lastname: Lee
mesh_terms: D050960:Aminomethyltransferase; D001483:Base Sequence; D005998:Glycine / Q000097:blood / Q000378:metabolism; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000172:deficiency* / Q000235:genetics; D020158:Hyperglycinemia, Nonketotic / Q000201:enzymology / Q000235:genetics*; D007231:Infant, Newborn; D008099:Liver / Q000378:metabolism; D008214:Lymphocytes / Q000097:blood; D025202:Molecular Diagnostic Techniques; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011296:Prenatal Diagnosis; D012189:Retrospective Studies
chemical_list: D019877:Hydroxymethyl and Formyl Transferases; D050960:Aminomethyltransferase; D005998:Glycine