Methylenetetrahydrofolate reductase deficiency in four siblings: A clinical, biochemical, and molecular study of the family

American Journal of Medical GeneticsVolume 91, Issue 5 p. 363-367 Methylenetetrahydrofolate reductase deficiency in four siblings: A clinical, biochemical, and molecular study of the family Carole Tonetti, Carole Tonetti Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceSearch for more papers by this authorAlain Burtscher, Alain Burtscher Cabinet de Pédiatrie, Munster, FranceSearch for more papers by this authorDominique Bories, Dominique Bories Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceSearch for more papers by this authorMichel Tulliez, Michel Tulliez Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceSearch for more papers by this authorJacqueline Zittoun, Corresponding Author Jacqueline Zittoun Jacqueline.zittoun@hmn.ap-hop-paris.fr Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceHôpital Henri Mondor 51, Av du Mal de Lattre de Tassigny, 94010 Créteil, FranceSearch for more papers by this author Carole Tonetti, Carole Tonetti Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceSearch for more papers by this authorAlain Burtscher, Alain Burtscher Cabinet de Pédiatrie, Munster, FranceSearch for more papers by this authorDominique Bories, Dominique Bories Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceSearch for more papers by this authorMichel Tulliez, Michel Tulliez Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceSearch for more papers by this authorJacqueline Zittoun, Corresponding Author Jacqueline Zittoun Jacqueline.zittoun@hmn.ap-hop-paris.fr Service d'Hématologie Biologique, Hôpital Henri Mondor, Créteil, FranceHôpital Henri Mondor 51, Av du Mal de Lattre de Tassigny, 94010 Créteil, FranceSearch for more papers by this author First published: 14 April 2000 https://doi.org/10.1002/(SICI)1096-8628(20000424)91:5<363::AID-AJMG9>3.0.CO;2-XCitations: 11Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract A diagnosis of methylenetetrahydrofolate reductase (MTHFR) deficiency was made in four sibs at different ages. The first three, including a pair of twins, had retarded psychomotor development, poor social contact, and seizures. Biologically, hyperhomocysteinemia and hypomethioninemia were found associated with low folate levels in serum and red cells, especially undetectable methyltetrahydrofolate in red cells. In the fourth child, prenatal diagnosis was not conclusive because of moderate decrease of enzymatic activity in chorionic villi and trophoblast. The girl was also affected, as shown by hyperhomocysteinemia and low folate levels found several days after birth. A 677C→T (Ala→Val) mutation was found in a homozygous state in the four children and in the father. Additionally, a second homozygous mutation, 1081C→T, changing an arginine to cysteine also was identified in all of the children, whereas the distantly consanguineous parents were heterozygous. This amino acid substitution affecting an arginine residue in a sequence located at the end of catalytic domain seems critical for the function of the enzyme. The difficulty of prenatal diagnosis is discussed given the variability found in enzymatic activity and in the clinical phenotypes. Am. J. Med. Genet. 91:363–367, 2000. © 2000 Wiley-Liss, Inc. Citing Literature Volume91, Issue524 April 2000Pages 363-367 RelatedInformation