Pathogenic mutations in the 5' untranslated region of BCS1L mRNA in mitochondrial complex III deficiency.

Abstract Mutations in the assembly chaperone BCS1L constitute a major cause of mitochondrial complex III deficiency. We studied the presence of BCS1L mutations in a complex III-deficient patient with metabolic acidosis, liver failure, and tubulopathy. A previously reported mutation, p.R56X, was identified in one BCS1L allele, and two novel heterozygous mutations, g.1181A > G and g.1164C > G, were detected in the second allele. The g.1181A > G mutation generated an alternative splicing site in the BCS1L transcript, causing a 19-nucleotides deletion in its 5′UTR region. Decreased BCS1L mRNA and protein levels, and a respiratory chain complex III assembly impairment, determine a pathogenic role for the novel BCS1L mutations.