Novel variants in PCCA and PCCB Genes in Chinese Patients with propionic acidemia

Published: 19 March 2020| Version 3 | DOI: 10.17632/dk3pfbb8f5.3
Qi Yang


Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by the deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC) and associated with pathogenic variants in either of the two genes, PCCA or PCCB. In the present study, three PA patients were diagnosed by using gas chromatography-mass spectrometry(GC-MS), tandem mass spectrometry (MS/MS) and Molecular diagnostic methods. All patients had onset in neonatal period. One patient died of infection and metabolic decompensation, and the other two had mild to moderate developmental delay/mental retardation. Mutation analysis of the PCCA gene identified compound heterozygous c.1288C>T(p.R430X) and c.2002G>A(p.G668R) in patient 1, homozygous c.1426C>T(p.R476X) in patient 2; mutation analysis of the PCCB gene identified compound heterozygousc.359_360del AT(p.Y120Cfs*40) and c.1398+1G>A in patient 3. Three novel mutations (c.1288C>T, c.359_360del AT and c.1398+1G>A were identified in PCCA and PCCB genes. Among them, in the PCCA gene, c.1288C>T(p.R430X) was a nonsense mutation, resulting in a truncated protein. c.359_360del AT was a frameshift mutation, leading to p.Y120Cfs*40 mutation of amino acid sequence in PCCB. c.1398+1G>A was a splicing mutation, causing skipping of the exons 13-14. In conclusion, the novel mutations of this study will expands the mutation spectrum of PA.


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The three unrelated patientswere clinically diagnosed with PA using via urine organic acid analysis by gas chromatography-mass spectrometry (GC-MS) and carnitine analysis by tandem mass spectrometry (MS/MS). Genomic DNA of all affected individuals was subjected to Sanger sequencing, and candidate mutations were verified by Sanger sequencing in all available family members.


Health Sciences