Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene

• Published in: American journal of medical genetics 2003-08, Vol.121A (2), p.126-131
• Main Authors: De Meirleir, Linda, Seneca, Sara, Damis, Eliane, Sepulchre, Brigitte, Hoorens, Anne, Gerlo, Erik, García Silva, M. Teres, Hernandez, Elena Martín, Lissens, Willy, Van Coster, Rudy
• Format: Article
• Language: English
• Subjects: ATPases Associated with Diverse Cellular Activities; Biological and medical sciences; Chromosome fragility (bloom syndrome, ataxia telangiectasia, fanconi anemia, x-linked mental retardation...); Codon, Nonsense; congenital lactic acidosis; Electron Transport Complex III - deficiency; Electron Transport Complex III - genetics; Fatal Outcome; Female; Gastroenterology. Liver. Pancreas. Abdomen; General aspects. Genetic counseling; Humans; Infant, Newborn; Liver - embryology; Liver - pathology; liver cholestasis; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical genetics; Medical sciences; Microscopy, Electron; mitochondrial encephalopathy; Mutation; Mutation, Missense; Other diseases. Semiology; OXPHOS deficiency; respiratory chain assembly genes; Sequence Analysis, DNA; Toni Fanconi Debré syndrome
• ISSN: 1552-4825; 0148-7299; 1552-4833; 1096-8628
• DOI: 10.1002/ajmg.a.20171

We investigated two siblings of a Spanish family presenting with congenital lactic acidosis. They had severe failure to thrive, liver dysfunction, and renal tubulopathy. An isolated biochemical complex III deficiency was detected in liver. A search for mutations in the human bc1 synthesis like (BCS1L) gene was undertaken. Direct sequencing revealed a missense mutation R45C and a nonsense mutation R56X, both located in exon 1 of BCS1L. The missense mutation in combination with a loss of function of the second allele is responsible for the isolated complex III deficiency in this family. © 2003 Wiley‐Liss, Inc.