A common mutation among blacks with mut− methylmalonic aciduria

Adjalla, Charles; Hosack, Angela; Matiaszuk, Nora; Rosenblatt, David S.

doi:10.1002/humu.1380110179

Cited by 17 publications

(11 citation statements)

References 20 publications

(27 reference statements)

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“…But we could not Wnd E117X mutation in Korean MMA patients. G717V was found in four African-American and one Ghanaian MMA patients with the mut ¡ phenotype [14]. The N219Y is a frequent mutation among mut 0 forms of MMA in Caucasian patients [15].…”

Section: Discussionmentioning

confidence: 92%

Mutation analysis of the MCM gene in Korean patients with MMA

Jung

Hwang

Park

et al. 2005

Molecular Genetics and Metabolism

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Section: Discussionmentioning

confidence: 92%

Mutation analysis of the MCM gene in Korean patients with MMA

Jung

Hwang

Park

et al. 2005

Molecular Genetics and Metabolism

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“…Position of asparagine 219 is indicated in bold and by a vertical arrow. Figure 3 View of the three-dimensional structure of the (b/a) 8 barrel of the human methylmalonyl-coenzyme A mutase model. The model was built on the basis of the experimental structure of the a chain of the Propionibacterium shermanii enzyme (PDB 1REQ).…”

Section: Resultsmentioning

confidence: 99%

“…The model was built on the basis of the experimental structure of the a chain of the Propionibacterium shermanii enzyme (PDB 1REQ). Domains are coloured as follows: blue for the (b/a) 8 barrel which binds the substrate (desulfo-CoA, as existing in the 1REQ structure, in pink), and green for the cofactor adenosylcobalamin (in the back). Asparagine 195 (corresponding to Asn219 in human) is shown in a CPK representation and is buried between the b-barrel structure and one of the a-helix surrounding this barrel.…”

Section: Resultsmentioning

confidence: 99%

“…2 To date, molecular analysis of mut MMA has revealed at least 49 different mutations 3 ± 7 demonstrating the highly pleiomorphic nature of this condition. Only two mutations are frequent: the first one (G717V) in African-Americans 8 and the second (E117X) in the Japanese population. 9,10 A three-dimensional model of the human MCM structure 11 has been deduced from the crystal structure of the corresponding enzyme in Propionibacterium shermanii, that shares 65% sequence identity with human MCM.…”

Section: Introductionmentioning

confidence: 99%

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N219Y, a new frequent mutation among mut° forms of methylmalonic acidemia in Caucasian patients

Acquaviva

Callebaut

et al. 2001

Eur J Hum Genet

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Mutations in the MUT locus encoding for the methylmalonyl-CoA mutase (MCM) apoenzyme are responsible for the mut forms of methylmalonic acidemia (MMA). To date, 49 different mutations have been identified in mut MMA. Only two frequent mutations have been reported in the Japanese population and in AfricanAmericans. Here we report a new missense mutation N219Y (731 A?T) which we found in five unrelated families of French and Turkish descent. All the patients exhibited a severe mut8 phenotype and three of them were homozygotes for N219Y. Direct involvement of the mutation in the loss of enzyme activity was demonstrated by mutagenesis and transient expression study. Mapping of the mutation onto a threedimensional model of human MCM constructed by homology with the Propionibacterium shermanii enzyme shows that it lies in a highly conserved secondary structure motif and might suggest impaired folding and/or poor stability compatible with the mut8 phenotype. Finally, a 1% N219Y carrier frequency was observed in a French anonymous control population. Thus, N219Y is the first frequent mut mutation to be reported in the Caucasian population.

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“…To date, more than 100 disease-causing mutations in the human MUT gene have been reported (Ledley and Rosenblatt 1997;Acquaviva et al 2005;Martinez et al 2005), most of which seem to be unique or restricted to only a few pedigrees. However, there have been reports of specific mutations among various ethic groups, including p.G717V in blacks (Adjalla et al 1998), p.N219Y in Caucasians (Acquaviva et al 2001), and p.R108C in Hispanics (Worgan et al 2006). Ogasawara et al (1994b) reported a relatively high incidence of p.E117X in Japanese patients and, more recently, Kobayashi et al (2006) identified the plural occurrence of each of six mutations (p.L494X, p.R93H, p.E117X, p.R369H, p.G648D, and c.385 + 5G > A) in another Japanese population.…”

Section: Introductionmentioning

confidence: 99%

Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia

et al. 2006

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Methylmalonic acidemia (MMA) is caused by a deficiency in the activity of L-methylmalonylCoA mutase (MCM), a vitamin B12 (or cobalamin, Cbl)-dependent enzyme. Apoenzyme-deficient MMA (mut MMA) results from mutations in the nuclear gene MUT. Most of the MUT mutations are thought to be private or restricted to only a few pedigrees. Our group elucidated the spectrum of mutations of Japanese mut MMA patients by performing mutation and haplotype analyses in 29 patients with mut MMA. A sequence analysis identified mutations in 95% (55/58) of the disease alleles. Five mutations were relatively frequent (p.E117X, c.385 + 5G > A, p.R369H, p.L494X, and p.R727X) and four were novel (p.M1V, c.753_753 + 5delGGTATA, c.1560G > C, and c.2098_2099delAT). Haplotype analysis suggested that all of the frequent mutations, with the exception of p.R369H, were spread by the founder effect. Among 46 Japanese patients investigated in the present and previous studies, 76% (70/92) of the mutations were located in exons 2, 6, 8, and 13. This finding -that a limited number of mutations account for most of the mutations in Japanese mut MMA patients -is in contrast with results of a previous study in Caucasian patients.

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A common mutation among blacks with mut− methylmalonic aciduria

Cited by 17 publications

References 20 publications

Mutation analysis of the MCM gene in Korean patients with MMA

Mutation analysis of the MCM gene in Korean patients with MMA

N219Y, a new frequent mutation among mut° forms of methylmalonic acidemia in Caucasian patients

Mutation and haplotype analyses of the MUT gene in Japanese patients with methylmalonic acidemia

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