Department of Neurology, Neuromuscular Research Center, Tampere University Hospital and University of Tampere, 33014, Tampere, Finland.
Institute of Myology, National Reference Center for Neuromuscular Disorders, University Hospital of Salpêtrière, UPMC, Paris, France.
J Neurol. 2019 Mar;266(3):680-690. doi: 10.1007/s00415-019-09187-2. Epub 2019 Jan 21.
Hereditary myopathy with early respiratory failure (HMERF) is caused by titin A-band mutations in exon 344 and considered quite rare. Respiratory insufficiency is an early symptom. A collection of families and patients with muscle disease suggestive of HMERF was clinically and genetically studied.
Altogether 12 new families with 19 affected patients and diverse nationalities were studied. Most of the patients were investigated using targeted next-generation sequencing; Sanger sequencing was applied in some of the patients and available family members. Histological data and muscle MRI findings were evaluated.
Three families had several family members studied while the rest were single patients. Most patients had distal and proximal muscle weakness together with respiratory insufficiency. Five heterozygous TTN A-band mutations were identified of which two were novel. Also with the novel mutations the muscle pathology and imaging findings were compatible with the previous reports of HMERF.
Our collection of 12 new families expands mutational spectrum with two new mutations identified. HMERF is not that rare and can be found worldwide, but maybe underdiagnosed. Diagnostic process seems to be complex as this study shows with mostly single patients without clear dominant family history.
遗传性肌病伴早期呼吸衰竭（HMERF）是由 344 号外显子中的肌联蛋白 A 带突变引起的，被认为较为罕见。呼吸功能不全是早期症状。本研究对具有 HMERF 特征的肌肉疾病的家系和患者进行了临床和遗传学研究。
共研究了 12 个新的家系，包括 19 名受累患者，这些患者来自不同的国家。大多数患者通过靶向下一代测序进行了检查；部分患者和可利用的家系成员进行了 Sanger 测序。评估了组织学数据和肌肉 MRI 结果。
3 个家系有多个家族成员接受了研究，其余均为单个患者。大多数患者同时存在远端和近端肌肉无力以及呼吸功能不全。发现了 5 个杂合性 TTN A 带突变，其中 2 个是新的。具有新突变的患者的肌肉病理学和影像学表现与 HMERF 的先前报道相符。
我们的 12 个新的家系的收集扩展了突变谱，其中鉴定出了 2 个新的突变。HMERF 并不罕见，可在世界各地发现，但可能被漏诊。正如本研究所示，诊断过程似乎很复杂，因为大多数患者为无明确显性家族史的单例患者。
