Novel variant p.(Ala102Thr) in SDHB causes mitochondrial complex II deficiency: Case report and review of the literature

Ann Hum Genet. 2020 Jul;84(4):345-351. doi: 10.1111/ahg.12377. Epub 2020 Mar 2.

Abstract

Leigh syndrome is a clinically and radiologically heterogeneous condition with approximately 75 genes, nuclear and mitochondrial, known to be implicated in its pathogenesis. Leigh syndrome due to complex II deficiency constitutes 2% to 7% of these cases. Previously, nine individuals with Leigh syndrome have been reported with pathogenic variants in SDHB, which encodes for the iron-sulfur cluster subunit of mitochondrial respiratory chain complex II. The proband presented with Leigh syndrome. Exome sequencing revealed a homozygous missense variant p.(Ala102Thr) in SDHB. In silico protein modeling of the wild-type and mutant proteins showed potentially decreased protein stability. We hereby report another individual with Leigh syndrome due to SDHB-related mitochondrial complex II deficiency and review the phenotype and genotype associated with this condition.

Keywords: Leigh disease; SDHB; mitochondrial diseases; mitochondrial respiratory chain complex II; oxidative phosphorylation.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Electron Transport Complex II / deficiency*
  • Electron Transport Complex II / genetics
  • Exome Sequencing
  • Homozygote
  • Humans
  • Infant
  • Male
  • Metabolism, Inborn Errors / genetics*
  • Mitochondrial Diseases / genetics*
  • Mutation, Missense
  • Protein Structure, Secondary
  • Succinate Dehydrogenase / genetics*

Substances

  • Electron Transport Complex II
  • SDHB protein, human
  • Succinate Dehydrogenase

Supplementary concepts

  • Mitochondrial Complex II Deficiency