The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism.

@article{Gallardo2001TheMB,
  title={The molecular basis of 3-methylcrotonylglycinuria, a disorder of leucine catabolism.},
  author={Mar{\'i}a Esther Gallardo and L. R. Desviat and J M Rodr{\'i}guez and Jorge Esparza-Gordillo and Celia P{\'e}rez-Cerd{\'a} and Bel{\'e}n P{\'e}rez and Pilar Rodr{\'i}guez-Pombo and Olga Criado and R Sanz and D. Holmes Morton and Kenneth Michael Gibson and Thuy Phan Le and Antonia Ribes and Santiago Rodr{\'i}guez de C{\'o}rdoba and Magdalena Ugarte and Miguel A. Pe{\~n}alva},
  journal={American journal of human genetics},
  year={2001},
  volume={68 2},
  pages={
          334-46
        }
}
3-Methylcrotonylglycinuria is an inborn error of leucine catabolism and has a recessive pattern of inheritance that results from the deficiency of 3-methylcrotonyl-CoA carboxylase (MCC). The introduction of tandem mass spectrometry in newborn screening has revealed an unexpectedly high incidence of this disorder, which, in certain areas, appears to be the most frequent organic aciduria. MCC, an heteromeric enzyme consisting of alpha (biotin-containing) and beta subunits, is the only one of the… 
The first case of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency responsive to biotin.
TLDR
This is the first patient with MCC deficiency caused by a heterozygote mutation and who demonstrated a substantial and sustained clinical and biochemical response to therapeutic doses of biotin, demonstrating that the main determinant of the outcome of even easily treatable metabolic diseases is timely diagnosis.
Molecular basis and functional characterization of human 3-methylcrotonyl-CoA carboxylase deficiency
TLDR
No clear correlation between genotype and phenotype is demonstrated suggesting that factors other than the genotype at the MCC loci have a major influence on the phenotype of MCC deficiency, and evidence that the missense mutation MCCA-p.R385S has a dominant negative effect on activity of wild type is provided.
Biochemical and molecular characterization of 3-Methylcrotonylglycinuria in an Italian asymptomatic girl
TLDR
The biochemical and molecular characterization of an Italian asymptomatic girl, positive for the newborn screening test, showed two mutations in the MCCC2 gene, an already described missense mutation, and a novel splicing mutation, which was characterized by functional studies.
Molecular mechanism of dominant expression in 3-methylcrotonyl-CoA carboxylase deficiency
TLDR
Evidence is presented that MCCA-R385S is a dominant negative allele leading to biochemical abnormalities and clinical symptoms in heterozygous individuals and that it is responsive to pharmacological doses of biotin in vivo.
A Case of Asymptomatic 3-methylcrotonylglycinuria Detected by Tandem Mass Spectrometry in Newborn Screening
TLDR
A case of a 43-day-old Korean asymptomatic girl with 3-Methylcrotonylglycinuria, detected by tandem mass spectrometry in newborn screening, and found 2 mutations in the MCC2 gene of this patient.
3-methylcrotonyl-CoA carboxylase deficiency: Clinical, biochemical, enzymatic and molecular studies in 88 individuals
TLDR
The data confirm that MCC deficiency, despite low penetrance, may lead to a severe clinical phenotype resembling classical organic acidurias, however, neither the genotype nor the biochemical phenotype is helpful in predicting the clinical course.
Isolated 3-methylcrotonyl-CoA carboxylase deficiency: evidence for an allele-specific dominant negative effect and responsiveness to biotin therapy.
TLDR
It is suggested that MCCA-R385S is a dominant negative allele and is biotin responsive in vivo, and reduces the MCC activity of cotransfected MccA-wild-type allele.
Cloning of the human MCCA and MCCB genes and mutations therein reveal the molecular cause of 3-methylcrotonyl-CoA: carboxylase deficiency.
TLDR
Sequence similarity with Glycine max and Arabidopsis thaliana genes encoding the two subunits of MCC permitted us to clone the cDNAs encoding the alpha- and beta-subunits of human MCC.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 28 REFERENCES
The molecular basis of human 3-methylcrotonyl-CoA carboxylase deficiency.
TLDR
It is shown that a series of 14 MCC-deficient probands defines two complementation groups, CG1 and 2, resulting from mutations in MCCB and MCCA, respectively, and that missense mutations in each result in loss of function.
Isolation of 3-methylcrotonyl-coenzyme A carboxylase from bovine kidney.
Molecular Characterization of the Non-biotin-containing Subunit of 3-Methylcrotonyl-CoA Carboxylase*
TLDR
The sequence of the Arabidopsis MCC-B gene has enabled the identification of animal paralogous Mcc-B cDNAs and genes, which may have an impact on the molecular understanding of the lethal inherited metabolic disorder methylcrotonylglyciuria.
Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients.
TLDR
Haplotype and mutational analysis of the HGO gene in 29 novel AKU chromosomes and characterization of five polymorphic sites in HGO provide insight into the origin and evolution of the various AKU alleles.
Assignment of the alpha and beta chains of human propionyl-CoA carboxylase to genetic complementation groups.
TLDR
It is suggested that pccA encodes the alpha chain of PCC while pccBC encodesThe beta chain, and furthermore predict that the beta chain is unstable in the absence of thealpha chain.
Overview of mutations in the PCCA and PCCB genes causing propionic acidemia
Propionic acidemia is an inborn error of metabolism caused by a deficiency of propionyl‐CoA carboxylase, a heteropolymeric mitochondrial enzyme involved in the catabolism of branched chain amino
Characterization of a Fungal Maleylacetoacetate Isomerase Gene and Identification of Its Human Homologue*
TLDR
The first characterization of a gene encoding a MAAI enzyme from any organism, the A. nidulans maiA gene, is reported here, and it is suggested that this compound(s) might be diagnostic for human MAAi deficiency.
The molecular basis of alkaptonuria
TLDR
The cloning of the human HGO gene is reported and it is established that it is the AKU gene, illustrating that HGO harbours missense mutations that cosegregate with the disease, and providing biochemical evidence that at least one of these missesense mutations is a loss–of–function mutation.
Fungal metabolic model for human type I hereditary tyrosinaemia.
TLDR
This work reports that fahA, the gene encoding Fah in the fungus Aspergillus nidulans, encodes a polypeptide showing 47.1% identity to its human homologue, and demonstrates that loss of homogentisate dioxygenase prevents the effects of a Fah deficiency.
Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes.
TLDR
Included cDNA clones coding for the alpha and beta polypeptides of human PCC and Restriction fragment length polymorphisms were identified that should prove useful to individual families at risk for propionic acidemia.
...
1
2
3
...