Clinical and diagnostic characteristics of complex III mitopathy due to novel BCS1L gene mutation in a Saudi patient

BMC Med Genomics. 2022 Mar 19;15(1):63. doi: 10.1186/s12920-022-01210-2.

Abstract

Background: Of the many types of mitochondrial diseases, mutations affecting BCS1L gene are regarded as chief cause of the defective mitochondrial complex-III, affecting normal mitochondrial functioning, and leading to wide variety of phenotypes.

Case presentation: In this case report we describe a novel genotype linked to a unique phenotype in a Saudi patient born of a consanguineous marriage. Detailed genetic analysis and whole genome sequencing identified a novel homozygous missense mutation in exon 5 c.712A > G (p.Ser328Gly) of the BCS1L gene, with predicted deleterious effects on the functioning AAA+-ATPase domain of the protein characterized by distinct clinical presentation associated with profound multisystem involvement, conductive hearing loss, absent external auditory canal, low posterior hair line, short neck, micro and retrognathia, over riding fingers, rocker bottom foot, small phallus with bilateral absent testis (empty scrotum) and intolerable lactic acidosis.

Conclusions: A pathogenic effect of this novel BCS1L mutation was reflected in the patient with his failure to thrive and a complex clinical and metabolic phenotype.

Keywords: BCS1L gene; Björnstad syndrome; Case report; Complex III; Gracile disease; Leigh syndrome; Metabolic acidosis; Mitochondrial disorders; Mitopathy.

Publication types

  • Case Reports

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / genetics
  • ATPases Associated with Diverse Cellular Activities / metabolism
  • Electron Transport Complex III* / genetics
  • Electron Transport Complex III* / metabolism
  • Humans
  • Male
  • Mitochondrial Diseases* / diagnosis
  • Mitochondrial Diseases* / genetics
  • Mitochondrial Diseases* / metabolism
  • Mutation
  • Saudi Arabia

Substances

  • BCS1L protein, human
  • ATPases Associated with Diverse Cellular Activities
  • Electron Transport Complex III