Case reports: three novel variants in PCCA and PCCB genes in Chinese patients with propionic acidemia
Open Access
- 6 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Medical Genetics
- Vol. 21 (1), 1-6
- https://doi.org/10.1186/s12881-020-01008-y
Abstract
Background: Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by the deficiency of the mitochondrial protein propionyl-CoA carboxylase (PCC) and is associated with pathogenic variants in either of the two genes PCCA or PCCB. The present study aimed to identify the genetic cause of three Chinese patients with PA. Case presentation: Three Chinese 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 the 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 that patient 1 carried the compound heterozygous c.1288C > T(p.R430X) and c.2002G > A(p.G668R), and patient 2 was homozygous for the c.1426C > T(p.R476X) mutation. Mutation analysis of the PCCB gene identified that patient 3 harbored the compound heterozygous mutations c.359_360del AT(p.Y120Cfs*40) and c.1398 + 1G > A. Among these mutations, three (c.1288C > T, c.359_360del AT and c.1398 + 1G > A) are novel. Conclusions: We reported three Chinese PA patients who had PCCA or PCCB mutants. 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 a p.Y120Cfs*40 change in the amino acid sequence in the PCCB protein. c.1398 + 1G > A was a splicing mutation, causing skipping of the exons 13–14. In conclusion, the novel mutations uncovered in this study will expands the mutation spectrum of PA.Keywords
Funding Information
- Guangxi Natural Science Foundation (2016GXNSFBA380191)
This publication has 17 references indexed in Scilit:
- The molecular landscape of propionic acidemia and methylmalonic aciduria in Latin AmericaJournal of Inherited Metabolic Disease, 2010
- Retrospective study of patients with suspected inborn errors of metabolism at Siriraj Hospital, Bangkok, Thailand (1997-2001).2005
- Functional characterization of PCCA mutations causing propionic acidemiaBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2002
- Nonsense-mediated mRNA decayin health and diseaseHuman Molecular Genetics, 1999
- Coding Sequence Mutations in the Alpha Subunit of Propionyl-CoA Carboxylase in Patients with Propionic AcidemiaMolecular Genetics and Metabolism, 1999
- A Perfect Message: RNA Surveillance and Nonsense-Mediated DecayCell, 1999
- Three novel splice mutations in the PCCA gene causing identical exon skipping in propionic acidemia patientsHuman Genetics, 1997
- Coding sequence of the precursor of the beta subunit of rat propionyl-CoA carboxylase.Proceedings of the National Academy of Sciences of the United States of America, 1986
- 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.Proceedings of the National Academy of Sciences of the United States of America, 1986
- Propionic acidemia: A clinical updateThe Journal of Pediatrics, 1981