BCS1Neonatal growth retardation and lactic acidosis initiated by novel mutation sites in L gene.
10.3760/cma.j.cn112150-20220610-00595
- Author:
Ming WANG
1
;
Dong Juan WANG
1
;
Yi SHU
1
;
Dan ZHU
1
;
Chao Wen YU
1
;
Xiao Yan HE
1
;
Lin ZOU
2
Author Information
1. Department of Clinical Molecular Medicine of Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China.
2. Department of Clinical Molecular Medicine of Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing 400014, China Clinical Research Unit of Children's Hospital in Shanghai Jiao Tong University School of Medicine, Institute of Pediatric Infection, Immunity, and Critical Care Medicine,Shanghai Jiao Tong University School of Medicine, Shanghai 200062, China.
- Publication Type:Journal Article
- MeSH:
Humans;
Acidosis, Lactic/genetics*;
Electron Transport Complex III/genetics*;
Retrospective Studies;
Mutation;
Growth Disorders;
ATPases Associated with Diverse Cellular Activities/genetics*
- From:
Chinese Journal of Preventive Medicine
2023;57(6):912-917
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.
