OBJECTIVE: To detect pathogenic variants in a pedigree affected with propionic acidemia (PA). METHODS: The proband was subjected to high-throughput next-generation sequencing. Suspected variants were validated by Sanger sequencing of his family members. mRNA was extracted from peripheral blood lymphocytes from the proband's father in order to verify the impact of the splicing variant by RT-PCR combined with Sanger sequencing. The pathogenicity of the missense variant was predicted by using PolyPhen-2, Mutation Taster, SIFT, COBALT and HOPE software. RESULTS: The proband was found to harbor compound heterozygous variants of the PCCB gene, namely c.184-2A>G and c.733G>A (p.G245S), which were respectively inherited from his father and mother. RT-PCR combined with Sanger sequencing confirmed skipping of exon 2 during transcription. Bioinformatic analysis indicated the c.733G>A (p.G245S) variant to be damaging. CONCLUSION The two variants of the PCCB gene probably underlay the disease in this patient. Above findings have enriched the spectrum of PCCB gene variants.
Exons ; Humans ; Mutation ; Mutation, Missense ; Pedigree ; Propionic Acidemia/genetics*

Objective: To verify the diagnosis of highly suspected glutaric academia type I for the cases found in neonatal screening and conduct related genetic analysis. Methods: In this research the clinical data of the children with glutaric academia type I were collected, and the diagnostic panels of inherited metabolism diseases with gene capture high-throughput sequencing technology were applied to perform genetic diagnosis in suspected cases. Sanger sequencing technology was also used to verify the genes of the members in this family. In addition, we searched a large number of relevant literatures for genetic analysis. Methods: In this research the clinical data of the children with glutaric academia type I were collected, and the diagnostic panels of inherited metabolism diseases with gene capture high-throughput sequencing technology were applied to perform genetic diagnosis in suspected cases. Sanger sequencing technology was also used to verify the genes of the members in this family. In addition, we searched a large number of relevant literatures for genetic analysis. Results: All the 3 cases were found to have complex heterozygous mutation sites of GCDH gene by gene sequencing technology. The mutation sites were c.109_110delCA and c.416C＞G in the first case, c.892G＞A and c.261_506-433delinsATA in the second case and c.1235C＞A and c.1244-2A＞C in the last case. Among them, c.261_506-433delinsATA and c.109_110delCA should be completely newly identified and never reported in literatures. All the mutation sites were verified to be inherited from their parents. Conclusion Next-generation sequencing technology can contribute to confirming the diagnosis of glutaric academia type I and provide reliable evidence for appropriate treatment and genetic counseling of this disease.