{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:23:55Z","timestamp":1778559835155,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2004,10,25]],"date-time":"2004-10-25T00:00:00Z","timestamp":1098662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:p>A frequent polymorphism in the gene coding for 5,10\u2010methylenetetrahydrofolate reductase is the substitution 677C\u2003&gt;\u2003T which produces a thermolabile and inefficient enzyme. Homozygosity for the 677C\u2003&gt;\u2003T allele is the most important determinant of hyperhomocys\u2010teinemia, when folic acid intake is reduced. Most studies on the relationship between the 677C\u2003&gt;\u2003T variant in the mother and defects in the offspring have focused on neural\u2010tube defects. This study is a retrospective case\u2010control investigation of hypoxic\u2010ischemic encephalopathy of the newborn (HIEN) with reference to the 677C\u2003&gt;\u2003T polymorphism as a genetic risk for this condition.<\/jats:p><jats:p>The prevalence of the 677C\u2003&gt;\u2003T allele was studied in 11 children with HIEN, their respective mothers, and 85 healthy individuals. Plasma homocysteine levels after fasting and methionine loading were determined in both mothers and controls.<\/jats:p><jats:p>Ten of 11 patients were evaluated using magnetic resonance (MR) imaging, and all showed multicystic encephalomalacia and severe brain vasculopathy. Seven mothers were homozygous and four heterozygous for the 677C\u2003&gt;\u2003T allele. Five of the children were homozygous and six heterozygous for this polymorphism. The variant allele frequency was higher in the group of mothers with affected children than in the controls and was associated with an increase in plasma homocysteine after methionine loading, in the group of mothers than in controls.<\/jats:p><jats:p>The 677C\u2003&gt;\u2003T mutation in mothers, either in a homozygous or heterozygous state, together with poor nutritional status (probable folate deficiency) may represent a risk factor for irreversible HIEN in the offspring.<\/jats:p>","DOI":"10.1111\/j.1399-0004.2004.00373.x","type":"journal-article","created":{"date-parts":[[2004,12,22]],"date-time":"2004-12-22T10:52:55Z","timestamp":1103712775000},"page":"69-80","source":"Crossref","is-referenced-by-count":22,"title":["Maternal mutation 677C\u2003&gt;\u2003T in the methylenetetrahydrofolate reductase gene associated with severe brain injury in offspring"],"prefix":"10.1111","volume":"67","author":[{"given":"R Dodelson","family":"De Kremer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Grosso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,12,22]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.59780238.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-195"},{"key":"e_1_2_6_4_2","first-page":"3897","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Rosenblatt DS","year":"2001"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a010290"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.2165\/00129785-200101030-00004"},{"key":"e_1_2_6_7_2","first-page":"35","article-title":"Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease","volume":"58","author":"Kluijtmans LAJ","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0595-111"},{"key":"e_1_2_6_9_2","first-page":"414","article-title":"Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase","volume":"43","author":"Kang SS","year":"1988","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.93.1.7"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.6.1157"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/128.8.1336"},{"key":"e_1_2_6_13_2","first-page":"230","article-title":"Differences in methylenetetrahydrofolate reductase genotype frequencies between whites and blacks","volume":"60","author":"Stevenson RE","year":"1997","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(97)00237-2"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/302015"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/301836"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005369109055"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2779(1998)4:4<239::AID-MRDD1>3.0.CO;2-W"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911113412006"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-2115(00)00426-7"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2000-9293"},{"key":"e_1_2_6_22_2","first-page":"35","volume-title":"Pediatric Neuroimaging","author":"Barkovich AJ","year":"1990"},{"key":"e_1_2_6_23_2","first-page":"193","volume-title":"Techniques in Diagnostic Human Biochemical Genetics. 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