Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism.

Article Details

Citation

Copy to clipboard

Lerner-Ellis JP, Dobson CM, Wai T, Watkins D, Tirone JC, Leclerc D, Dore C, Lepage P, Gravel RA, Rosenblatt DS

Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism.

Hum Mutat. 2004 Dec;24(6):509-16.

PubMed ID

15523652 [ View in PubMed

]

Abstract

Mutations in the MMAA gene on human chromosome 4q31.21 result in vitamin B12-responsive methylmalonic aciduria (cblA complementation group) due to deficiency in the synthesis of adenosylcobalamin. Genomic DNA from 37 cblA patients, diagnosed on the basis of cellular adenosylcobalamin synthesis, methylmalonyl-coenzyme A (CoA) mutase function, and complementation analysis, was analyzed for deleterious mutations in the MMAA gene by DNA sequencing of exons and flanking sequences. A total of 18 novel mutations were identified, bringing the total number of mutations identified in 37 cblA patients to 22. A total of 13 mutations result in premature stop codons; three are splice site defects; and six are missense mutations that occur at highly conserved residues. Eight of these mutations were common to two or more individuals. One mutation, c.433C>T (R145X), represents 43% of pathogenic alleles and a common haplotype was identified. Restriction endonuclease or heteroduplex diagnostic tests were designed to confirm mutations. None of the sequence changes identified in cblA patients were found in 100 alleles from unrelated control individuals.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cyanocobalamin	Methylmalonic aciduria type A protein, mitochondrial	Protein	Humans	Unknown	Binder	Details

Polypeptides

Name	UniProt ID
Methylmalonic aciduria type A protein, mitochondrial	Q8IVH4	Details