Novel compound heterozygous SUCLG1 variants may contribute to mitochondria DNA depletion syndrome-9.

Autor: Chen YM; Department of Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Chen W; Department of Radiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Xu Y; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Lu CS; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Zhu MM; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Sun RY; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Wang Y; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Chen Y; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Shi J; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China., Wang D; Department of Pediatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2022 Sep; Vol. 10 (9), pp. e2010. Date of Electronic Publication: 2022 Jun 28.
DOI: 10.1002/mgg3.2010
Abstrakt: Background: Succinate-CoA ligase/synthetase (SCS) deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Variants in SUCLG1, the nuclear gene encoding the alpha subunit of the SCS enzyme playing a pivotal role in maintaining mtDNA integrity and stability, are associated with mitochondrial DNA depletion syndrome 9 (MTDPS9).
Methods: In this study, we reported an infant with clinical features of MTDPS9 from China. Whole exome sequencing (WES) was used to identify the genetic cause. Bioinformatic analysis and mtDNA level detection were performed to assess pathogenicity.
Results: The proband manifested with hypotonia, lactic acidosis, mild methylmalonic aciduria, hearing loss and psychomotor retardation. WES identified new compound heterozygous SUCLG1 variants of c.601A>G (p.R201G) in exon 6 and c.871G>C (p.A291P) in exon 8. Computational analysis predicted that these missense variants might alter structure stability and mitochondrial translocation of SUCLG1. qRT-PCR showed 68% depletion of mtDNA content in proband as compared to controls.
Conclusion: Novel compound heterozygous variants c.601A>G (p.R201G) and c.871G>C (p.A291P) in SUCLG1 may cause MTDPS9 in this family. Our finding should be helpful for molecular diagnosis, genetic counseling and clinical management of SCS deficiency disorders.
(© 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje