Toone Jennifer R, Applegarth Derek A, Levy Harvey L, Coulter-Mackie Marion B, Lee Gary
Department of Pediatrics, University of British Columbia, and Biochemical Genetics Laboratory, B.C.'s Children's Hospital, Vancouver, BC, Canada.
Mol Genet Metab. 2003 Aug;79(4):272-80. doi: 10.1016/s1096-7192(03)00115-x.
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.
