Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation.

Raff, Martin; Crane, Ana M.; Jansen, Ruud; Ledley, Fred D.; Rosenblatt, David S.

doi:10.1172/jci114972

Cited by 36 publications

(24 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…incorporation in the presence and absence of OHCbl and by complementation analysis as previously described (Raff et al, 1991). Exon XI11 of the genomic DNA from both patients' fibroblasts was amplified by polymerase chain reaction (PCR), using two oligonucleotide primers within intron XI1 (#80) and exon XI11 (#33) as previously described (Crane et al, 1992).…”

Section: S249mentioning

confidence: 99%

A common mutation among blacks with mut− methylmalonic aciduria

et al. 1998

View full text Add to dashboard Cite

Section: S249mentioning

confidence: 99%

A common mutation among blacks with mut− methylmalonic aciduria

et al. 1998

View full text Add to dashboard Cite

“…Patients were assigned to complementation groups (cblA-H, mut) based on the outcome of cell fusion experiments and the apparent biochemical defect involved [16][17][18]. The cblE complementation group was shown to result from defective reactivation of methionine synthase [19].…”

Section: Introductionmentioning

confidence: 99%

Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase

Elmore

Leclerc

et al. 2007

Molecular Genetics and Metabolism

122

View full text Add to dashboard Cite

Hyperhomocyst(e)inemia is a metabolic derangement that is linked to the distribution of folate pools, which provide one-carbon units for biosynthesis of purines and thymidylate and for remethylation of homocysteine to form methionine. In humans, methionine synthase deficiency results in the accumulation of methyltetrahydrofolate at the expense of folate derivatives required for purine and thymidylate biosynthesis. Complete ablation of methionine synthase activity in mice results in embryonic lethality. Other mouse models for hyperhomocyst(e)inemia have normal or reduced levels of methyltetrahydrofolate and are not embryonic lethal, although they have decreased ratios of AdoMet/AdoHcy and impaired methylation. We have constructed a mouse model with a gene trap insertion in the Mtrr gene specifying methionine synthase reductase, an enzyme essential for the activity of methionine synthase. This model is a hypomorph, with reduced methionine synthase reductase activity, thus avoiding the lethality associated with the absence of methionine synthase activity. Mtrr gt/gt mice have increased plasma homocyst(e)ine, decreased plasma methionine, and increased tissue methyltetrahydrofolate. Unexpectedly, Mtrr gt/gt mice do not show decreases in the AdoMet/AdoHcy ratio in most tissues. The different metabolite profiles in the various genetic mouse models for hyperhomocysteinemia may be useful in understanding biological effects of elevated homocyst(e)ine.

show abstract

“…He had a trial of cyanocobalamin (1,000 mg/day IV for >1 month), but showed no lowering of methylmalonate. His fibroblasts were shown to be in the mut 0 complementation group in the Rosenblatt laboratory (Raff et al 1991), and he was subsequently documented to be homozygous for the c.322C>T (p.Arg108Cys) mutation in the MUT gene, previously shown to cause MMA (Worgan et al 2006). For several years he was well controlled with management including dietary restriction of propiogenic amino acids and large intravenous doses of carnitine.…”

Section: Patientsmentioning

confidence: 99%

Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia

et al. 2015

View full text Add to dashboard Cite

Liver transplantation has been reported in patients with methylmalonic acidemia (MMA), but longterm outcome is controversial. Many patients with other approved indications for liver transplantation die before donor grafts are available. A 28-year-old man with MMA underwent cadaveric liver transplantation. His liver was used as a domino graft for a 61-year-old man with primary sclerosing cholangitis, who had low priority on the transplant waiting list. Surgical outcome was successful, and after transplantation both patients have excellent graft function. The patient with MMA showed substantial decrease in methylmalonate in urine (from 5,277 AE 1,968 preoperatively to 1,068 AE 384 mmol/mol creatinine) and plasma (from 445.9 AE 257.0 to 333.3 AE 117.7 mmol/l) over >1-year follow-up, while dietary protein intake increased from 0.6 to 1.36 AE 0.33 g/kg/day. The domino recipient maintained near-normal levels of plasma amino acids but did develop elevated methylmalonate in blood and urine while receiving an unrestricted diet (peak plasma methylmalonate 119 mmol/l and urine methylmalonate 84-209 mmol/mol creatinine, with 1.0-1.9 g/kg/day protein). Neither patient demonstrated any apparent symptoms of MMA or metabolic decompensation during the postoperative period or following discharge.Conclusion: Liver transplantation substantially corrects methylmalonate metabolism in MMA and greatly attenuates the disease. In this single patient experience, a liver from a patient with MMA functioned well as domino graft although it did result in subclinical methylmalonic acidemia and aciduria in the recipient. Patients with MMA can be considered as domino liver donors for patients who might otherwise spend long times waiting for liver transplantation.

show abstract

Genetic characterization of a MUT locus mutation discriminating heterogeneity in mut0 and mut- methylmalonic aciduria by interallelic complementation.

Abstract: Clin. Invest. 1991. 87:203-207.).

Cited by 36 publications

References 9 publications

A common mutation among blacks with mut− methylmalonic aciduria

A common mutation among blacks with mut− methylmalonic aciduria

Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase

Successful Domino Liver Transplantation from a Patient with Methylmalonic Acidemia

Contact Info

Product

Resources

About