Pathogenic mutations in the 5' untranslated region of BCS1L mRNA in mitochondrial complex III deficiency.
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.
Gil-Borlado
M Carmen
MC
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Spain.
González-Hoyuela
Maritza
M
Blázquez
Alberto
A
García-Silva
M Teresa
MT
Gabaldón
Toni
T
Manzanares
Javier
J
Vara
Julia
J
Martín
Miguel A
MA
Seneca
Sara
S
Arenas
Joaquín
J
Ugalde
Cristina
C
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
D020121:5' Untranslated Regions; C435491:BCS1L protein, human; D012333:RNA, Messenger; D000074183:ATPases Associated with Diverse Cellular Activities; D014450:Electron Transport Complex III