title: 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.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Gil-Borlado
authors.forename: Maritza
authors.initials: M
authors.lastname: González-Hoyuela
authors.forename: Alberto
authors.initials: A
authors.lastname: Blázquez
authors.forename: M Teresa
authors.initials: MT
authors.lastname: García-Silva
authors.forename: Toni
authors.initials: T
authors.lastname: Gabaldón
authors.forename: Javier
authors.initials: J
authors.lastname: Manzanares
authors.forename: Julia
authors.initials: J
authors.lastname: Vara
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martín
authors.forename: Sara
authors.initials: S
authors.lastname: Seneca
authors.forename: Joaquín
authors.initials: J
authors.lastname: Arenas
authors.forename: Cristina
authors.initials: C
authors.lastname: Ugalde
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000074183:ATPases Associated with Diverse Cellular Activities; D001483:Base Sequence; D014450:Electron Transport Complex III / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D020121:5' Untranslated Regions; C435491:BCS1L protein, human; D012333:RNA, Messenger; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III