Berger Itai, Hershkovitz Eli, Shaag Avraham, Edvardson Simon, Saada Ann, Elpeleg Orly
Pediatric Neurology Unit, Hadassah-Hebrew University Medical Center, Jerusalem.
Ann Neurol. 2008 Mar;63(3):405-8. doi: 10.1002/ana.21332.
Complex I deficiency is the most common respiratory chain defect, clinically manifesting by severe neonatal lactic acidosis, Leigh's disease, or various combinations of cardiac, hepatic, and renal disorders. Using homozygosity mapping, we identified a splice-site mutation in the NDUFA11 gene in six patients from three unrelated families. The patients presented with encephalocardiomyopathy or fatal infantile lactic acidemia. The mutation is predicted to abolish the first transmembrane domain of the gene product, thereby destabilizing the enzymatic complex. Mutation analysis of the NDUFA11 is warranted in isolated complex I deficiency presenting with infantile lactic acidemia or encephalocardiomyopathy.
复合体I缺乏是最常见的呼吸链缺陷，临床表现为严重的新生儿乳酸酸中毒、 Leigh病，或心脏、肝脏和肾脏疾病的各种组合。通过纯合性定位，我们在来自三个无关家族的六名患者中鉴定出NDUFA11基因的一个剪接位点突变。这些患者表现为脑心肌病或致命性婴儿乳酸血症。该突变预计会消除基因产物的第一个跨膜结构域，从而使酶复合物不稳定。对于表现为婴儿乳酸血症或脑心肌病的孤立性复合体I缺乏症，有必要对NDUFA11进行突变分析。
