[A novel compound heterozygous mutation causing 3-methylcrotonyl-CoA carboxylase deficiency]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2016 Oct;33(5):657-61. doi: 10.3760/cma.j.issn.1003-9406.2016.05.017.
[Article in Chinese]

Abstract

Objective: To explore the molecular mechanism for a boy suspected with 3-methylcrotonyl-CoA carboxylase deficiency by neonatal screening.

Methods: PCR and Sanger sequencing were used to identify potential mutations of MCCC1 and MCCC2 genes. SIFT and Polyphen-2 software was used to predict the effect of variant on the protein function and conservation of the variant across various species. Human Splicing Finder and Swiss-PdbViewer4.1.0 were applied to analyze the possible mechanism of the variant.

Results: For the proband, a compound heterozygous mutation was discovered in the MCCC1 gene, namely c.539G>T (p.G180V) and c.704_711del (p.A235Vfs*4), which were inherited from his father and mother, respectively. The two mutations have disrupted the protein conformation, which in turn may impact the function of MCC protein.

Conclusion: The compound heterozygous mutations of the MCCC1 gene may contribute to the 3-methylcrotonyl-CoA carboxylase deficiency manifested by the patient.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Carbon-Carbon Ligases / chemistry
  • Carbon-Carbon Ligases / deficiency*
  • Carbon-Carbon Ligases / genetics*
  • DNA Mutational Analysis
  • Heterozygote
  • Humans
  • Infant, Newborn
  • Male
  • Models, Molecular
  • Mutation*
  • Neonatal Screening / methods
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Urea Cycle Disorders, Inborn / diagnosis
  • Urea Cycle Disorders, Inborn / genetics*

Substances

  • Carbon-Carbon Ligases
  • methylcrotonoyl-CoA carboxylase 1, human