Identification of two novel variants of the PCCB gene in a pedigree affected with propionic acidemia.
10.3760/cma.j.cn511374-20200120-00042
- VernacularTitle:一个丙酸血症家系的
PCCB基因两个新变异鉴定
- Author:
Qigang ZHANG
1
;
Guanglai FAN
;
Shu ZHANG
;
Yuefang LIU
;
Wenjie ZHANG
;
Qiong PAN
Author Information
1. Department of Neonatal Disease Screening, Huai'an Maternal and Child Health-Care Hospital, Huai'an, Jiangsu 223002, China. jonespan@163.com.
- Publication Type:Journal Article
- MeSH:
Exons;
Humans;
Mutation;
Mutation, Missense;
Pedigree;
Propionic Acidemia/genetics*
- From:
Chinese Journal of Medical Genetics
2021;38(3):251-254
- CountryChina
- Language:Chinese
-
Abstract:
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.
