caa a22 4500 397574800 CHVBK 20180308164852.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.1867 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.1867 Human Methionine Synthase: cDNA Cloning and Identification of Mutations in Patients of the cblG Complementation Group of Folate/Cobalamin Disorders [Elektronische Daten] [D. Leclerc, E. Campeau, P. Goyette, C. E. Adjalla, B. Christensen, M. Ross, P. Eydoux, D. S. Rosenblatt, R. Rozen, R. A. Gravel] Methionine synthase catalyzes the remethylation of homocysteine to methionine in a methylcobalamin-dependent reaction. We used specific regions of homology within the methionine synthase sequences of several lower organisms to clone a human methionine synthase cDNA by a combination of RT-PCR and inverse PCR. The enzyme is 1265 amino acids in length and contains the seven residue structure-based sequence fingerprint identified for cobalamin-containing enzymes. The gene was localized to chromosome 1q43 by the FISH technique. We have identified one missense mutation and a 3 bp deletion in patients of the cbIG complementation group of inherited homocysteine/folate disorders by SSCP and sequence analysis, as well as an amino acid substitution present in high frequency in the general population. We discuss the possibility that a mild deficiency of methionine synthase activity could be associated with mild hyperhomocysteinemia, a risk factor for cardiovascular disease and possibly neural tube defects. © 1993 Oxford University Press Leclerc D. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Campeau E. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Goyette P. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Adjalla C. E. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Christensen B. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Ross M. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Eydoux P. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Rosenblatt D. S. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Rozen R. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Gravel R. A. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 1867-1874 0964-6906 5:12<1867 1996 5 hmg https://doi.org/10.1093/hmg/5.12.1867 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.1867 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Leclerc D. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Campeau E. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Goyette P. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Adjalla C. E. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Christensen B. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Ross M. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Eydoux P. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Rosenblatt D. S. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Rozen R. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 700 1- Gravel R. A. MRC Group in Medical Genetics, Departments of Pediatrics, Human Genetics, Biology, Pathology and Medicine, McGill University, Montreal, Quebec, H3Z 2Z3, Canada aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 1867-1874 0964-6906 5:12<1867 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford