Gil-Borlado M Carmen, González-Hoyuela Maritza, Blázquez Alberto, García-Silva M Teresa, Gabaldón Toni, Manzanares Javier, Vara Julia, Martín Miguel A, Seneca Sara, Arenas Joaquín, Ugalde Cristina
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U723, Spain.
Mitochondrion. 2009 Sep;9(5):299-305. doi: 10.1016/j.mito.2009.04.001. Epub 2009 Apr 21.
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.
组装伴侣蛋白BCS1L的突变是线粒体复合物III缺乏症的主要原因。我们研究了一名患有代谢性酸中毒、肝衰竭和肾小管病的复合物III缺乏症患者中BCS1L突变的情况。在一个BCS1L等位基因中鉴定出一个先前报道的突变p.R56X，在第二个等位基因中检测到两个新的杂合突变g.1181A>G和g.1164C>G。g.1181A>G突变在BCS1L转录本中产生了一个可变剪接位点，导致其5'UTR区域出现19个核苷酸的缺失。BCS1L mRNA和蛋白质水平降低以及呼吸链复合物III组装受损，确定了新的BCS1L突变的致病作用。
