{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:35:55Z","timestamp":1768264555041,"version":"3.49.0"},"reference-count":22,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Glycine encephalopathy, or nonketotic hyperglycinaemia (NKH; McKusick 238300) is a severe autosomal recessive disease due to a defect in the glycine cleavage system (GCS), which is a complex of four subunits: P\u2010, T\u2010, H\u2010 and L\u2010proteins. A P\u2010protein (glycine decarboxylase or GLDC) deficiency was reported in about 80% of NKH patients. We performed mutation analysis of the complete coding sequence of the <jats:italic>GLDC<\/jats:italic> gene in 28 unrelated patients with neonatal NKH using denaturing high\u2010performance liquid chromatography (DHPLC) and sequencing. Forty different gene alterations were identified, confirming the large molecular heterogeneity of the <jats:italic>GLDC<\/jats:italic> gene. Eighteen alterations were clearly disease\u2010causing: two large deletions, four one\u2010base deletions (c.28delC, c.1175delC, c.2186delC, c.2422delA), one 1\u2010base insertion (c.1002_1003insT), one 4\u2010base insertion (c.1285_1286insCAAA), one insertion\/deletion (c.2153_2155delinsTCCTGGTTTA), five nonsense mutations (p.E153X, p.R236X, p.E270X, p.R337X, p.R424X) and four splice site mutations (c.861+1G &gt; T, c.1402\u22121C &gt; G, c.2316\u22121G &gt; A, c.2919+1G &gt; A). Additionally, we identified one intronic mutation outside the consensus splice sites (c.2838+5G &gt; A) and 21 nucleotide substitutions leading to amino acid change (including three previously described mutations: p.T269M, p.R461Q, p.G771R), the pathogenicity of which should be confirmed by expression studies (p.S132W, p.Y138F, p.G171A, p.T187K, p.R212K, p.T269M, p.R373W, p.I440N, p.R461Q, p.N533Y, p.C644F, p.H651R, p.V705M, p.N732K, p.G771R, p.H775R, p.T830M, p.A841P, p.D880V, p.S957P and p.R966G). Mutation analysis allowed us to identify sequence alterations in both alleles for 19 patients and in one allele for 7 patients One patient was carrying three mutations (p.Y138F, p.T269M and p.E153X) and one patient was carrying two amino acid substitutions on the same allele (p.V705M and p.R212K) and an unidentified mutation on the other allele. No mutation could be found in two patients, suggesting possible defects in the H\u2010protein or gene alterations that could not be identified by our technique. The potential use of genotype determination for prenatal diagnosis is emphasized.<\/jats:p>","DOI":"10.1007\/s10545-006-0202-6","type":"journal-article","created":{"date-parts":[[2006,4,6]],"date-time":"2006-04-06T21:48:10Z","timestamp":1144360090000},"page":"135-142","source":"Crossref","is-referenced-by-count":35,"title":["Genetic heterogeneity of the <i>GLDC<\/i> gene in 28 unrelated patients with glycine encephalopathy"],"prefix":"10.1002","volume":"29","author":[{"given":"C.","family":"Conter","sequence":"first","affiliation":[{"name":"Centre d'Etude des Maladies M\u00e9taboliques H\u00f4pital Debrousse Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. O.","family":"Rolland","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Maladies M\u00e9taboliques H\u00f4pital Debrousse Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Cheillan","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Maladies M\u00e9taboliques H\u00f4pital Debrousse Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Maladies M\u00e9taboliques H\u00f4pital Debrousse Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Maire","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Maladies M\u00e9taboliques H\u00f4pital Debrousse Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Froissart","sequence":"additional","affiliation":[{"name":"Centre d'Etude des Maladies M\u00e9taboliques H\u00f4pital Debrousse Lyon France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,2]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(200005)20:5<367::AID-PD814>3.0.CO;2-E"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000031222.38328.59"},{"key":"e_1_2_1_4_1","first-page":"2065","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Hamosh A","year":"2001"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110284"},{"issue":"2","key":"e_1_2_1_6_1","article-title":"Natural history of glycine encephalopathy in 65 patients.","volume":"26","author":"Hoover\u2010Fong JE","year":"2003","journal-title":"J Inherit Metab 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