Novel mutations of PCCA and PCCB genes found by whole-exome sequencing related to propionic acidemia patients

Propionic acidemia (PROP) is an autosomal recessive inherited metabolic deficiency caused by multimeric mitochondrial enzyme propionyl‐coenzyme A (CoA) carboxylase (PCC). PCC enzyme contains a and b subunits, encoded by the PCCA and PCCB genes that mutations in both subunits are related to propionic acidemia. About 50% of disease-causing variants have been found in PCCA and most mutations related to propionic acidemia are missense mutations. The present study involves three families that are suspicious to hereditary propionic acidemia syndrome. The first family has four, the second family has one, and the third family has two passed-away children. All these families were diagnosed with the same clinical conditions such as poor feeding, vomiting, hypotonia, and lethargy. In the process of finding and confirming the mutation, pathological tests and whole-exome sequencing and sanger sequencing were done. In order to pathological tests and whole-exome sequencing, this is the first report of three novel variants related to propionic acidemia: 1. Novel pathogenic homozygous NM_000532.5: c.503_505del: p.Glu168del mutation of the PCCB exon5 gene, 2. Novel pathogenic homozygous splicing NM_000282:c.1900- 1G>A mutation of PCCA exon22 and exon21, 3. Novel compound heterozygous pathogenic NM_000532.5: c.503_505del: p.Glu168del and likely pathogenic NM_000532.5:c.539T>C: P.F180S mutation of the PCCB exon5 gene. The study shows that PCCA and PCCB have a great role in hereditary propionic acidemia and the results of the present study may be of importance in genetic counseling and finding the best treatment of this syndrome. DOI: http://dx.doi.org/10.5281/zenodo.737427