Morel Godelieve, Bannwarth Sylvie, Chaussenot Annabelle, Cano Aline, Fragaki Konstantina, Ait-El-Mkadem Samira, Rouzier Cecile, De Paula Andre Maues, Chabrol Brigitte, Paquis-Flucklinger Veronique
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France.
Department of Medical Genetics, National Centre for Mitochondrial Diseases, Nice Teaching Hospital, France; Nice Sophia-Antipolis University, IRCAN, CNRS, INSERM, UMR 7284 & U1081, 06107 Nice, France.
Neuromuscul Disord. 2016 Dec;26(12):885-889. doi: 10.1016/j.nmd.2016.09.012. Epub 2016 Sep 16.
An 11-year-old boy with psychomotor delay, exercise intolerance, ptosis and growth delay had a muscle biopsy showing typical mitochondrial alterations (60% of ragged-red fibers and 90% of cytochrome-c oxidase-deficient fibers). Next-generation sequencing revealed a novel heteroplasmic mutation (m.15958A>T) in the MTTP gene that encodes tRNA. The mutation was not present in the accessible non-muscle tissues of the patient's asymptomatic mother. Mutations in the rarely affected MTTP gene are responsible for different clinical presentations. We report the third early-onset case associated with a mutation in this gene. The severity of myopathy is likely related to the high mutation rate (96%) found in the patient's muscle. The clinical heterogeneity associated with MTTP mutations illustrates the value of the next-generation sequencing in routine diagnosis of mitochondrial diseases.
一名11岁男孩，有精神运动发育迟缓、运动不耐受、上睑下垂和生长发育迟缓，肌肉活检显示典型的线粒体改变（60%为破碎红纤维，90%为细胞色素c氧化酶缺乏纤维）。二代测序揭示了编码tRNA的MTTP基因中一个新的异质性突变（m.15958A>T）。该突变在患者无症状母亲的可获取非肌肉组织中不存在。很少受影响的MTTP基因中的突变导致了不同的临床表现。我们报告了第三例与该基因突变相关的早发病例。肌病的严重程度可能与患者肌肉中发现的高突变率（96%）有关。与MTTP突变相关的临床异质性说明了二代测序在线粒体疾病常规诊断中的价值。
