[Genetic analysis of a child with combined oxidative phosphorylation deficiency 14 due to variant of FARS2 gene]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Dec 10;39(12):1393-1397. doi: 10.3760/cma.j.cn511374-20210731-00644.
[Article in Chinese]

Abstract

Objective: To explore the genetic etiology for an infant featuring convulsive status epilepticus, developmental delay and elevated plasma lactate.

Methods: Whole exome sequencing and mitochondrial D-loop sequencing were carried out for the infant. Candidate variants were verified by Sanger sequencing. Previously reported FARS2 gene variants were searched from the PubMed, Wanfang and CNKI databases.

Results: The infant was found to harbor compound heterozygous variants of the FARS2 gene, namely c.925G>A (p.G309S) and c.405C>A (p.H135Q), which were inherited from its mother and father, respectively. The former has been recorded by the HGMD as a pathogenic variant, whilst the latter was predicted to be likely pathogenic based on the guidelines of the American College of Medical Genetics and Genomics. A total of 30 COXPD14 cases were retrieved from the literature, with common mutations including missense variants, in-frame deletions, splice-site variants and large deletions.

Conclusion: The common manifestations of COXPD14 have included developmental delay (96%), status epilepticus (97%) and increased lactic acid (96%). The compound heterozygous variants of the FARS2 gene probably underlay the disorder in this child.

Publication types

  • Case Reports
  • English Abstract

MeSH terms

  • Exome Sequencing
  • Female
  • Genetic Testing
  • Humans
  • Infant
  • Mitochondrial Diseases*
  • Mitochondrial Proteins / genetics
  • Phenylalanine-tRNA Ligase*
  • Status Epilepticus*

Substances

  • FARS2 protein, human
  • Mitochondrial Proteins
  • Phenylalanine-tRNA Ligase