ADSSL1 myopathy is the most common nemaline myopathy in Japan with variable clinical features
ADSSL1 myopathy is the most common nemaline myopathy in Japan with variable clinical features
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DOI：
10.1212/wnl.0000000000010237
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发表时间：
2020-09-15
期刊：
影响因子：
9.9
通讯作者：
Nishino, Ichizo
中科院分区：
文献类型：
--
作者：
Saito, Yoshihiko;Nishikawa, Atsuko;Nishino, Ichizo
目的 阐明日本 ADSSL1 肌病的患病率并确定该病的临床病理特征。方法 我们在我们的存储库中搜索了 1978 年 1 月至 2019 年 3 月肌病患者的 ADSSL1 变异，并评估了变异患者的临床病理特征。结果我们鉴定出来自 59 个家庭的 63 名患者患有 ADSSL1 双等位基因变异。在鉴定的 7 个不同变异中，c.781G>A 和 c.919delA 分别占等位基因的 53.2% 和 40.5%，表明存在共同的创始人，而其他 5 个变异是新的。大多数已确定的患者在青春期表现出比之前报道的患者更多变的肌肉症状，包括近端和/或远端腿部肌肉、舌头、咬肌、膈肌和椎旁肌的症状。 63 名患者中有 26 名出现吞咽困难并伴有咀嚼功能障碍； 48 名患者中有 12 名患上肥厚型心肌病； 34 名患者中有 26 名在后期出现限制性通气功能不全。放射学检查显示，所有患者均观察到股外侧肌、腓肠肌和比目鱼肌周围有脂肪浸润。病理学上，所有患者中普遍观察到线状小体以及脂滴增加和肌原纤维紊乱，这表明该疾病可能被归类为线状肌病。这一发现表明，ADSSL1 肌病是我们中心所有可基因诊断的线状肌病中最常见的。结论 ADSSL1 肌病的特点是比之前报道的表现更加多样化。它是我们中心所有可基因诊断的线状肌病中最常见的，尽管脂滴轻度增加也是经常观察到的特征。
Objective To elucidate the prevalence of Japanese ADSSL1 myopathy and determine the clinicopathologic features of the disease. Methods We searched forADSSL1variants in myopathic patients from January 1978 to March 2019 in our repository and assessed the clinicopathologic features of patients with variants. Results We identified 63 patients from 59 families with biallelic variants ofADSSL1. Among the 7 distinct variants identified, c.781G>A and c.919delA accounted for 53.2% and 40.5% of alleles, respectively, suggesting the presence of common founders, while the other 5 were novel. Most of the identified patients displayed more variable muscle symptoms, including symptoms in the proximal and/or distal leg muscles, tongue, masseter, diaphragm, and paraspinal muscles, in adolescence than previously reported patients. Dysphagia with masticatory dysfunction developed in 26 out of 63 patients; hypertrophic cardiomyopathy developed in 12 out of 48 patients; and restrictive ventilatory insufficiency developed in 26 out of 34 patients in later stages. Radiologically, fat infiltration into the periphery of vastus lateralis, gastrocnemius, and soleus muscles was observed in all patients. Pathologically, nemaline bodies in addition to increased lipid droplets and myofibrillar disorganization were commonly observed in all patients, suggesting that the disease may be classified as nemaline myopathy. This finding revealed thatADSSL1myopathy is the most frequent among all genetically diagnosable nemaline myopathies in our center. Conclusions ADSSL1 myopathy is characterized by more variable manifestations than previously reported. It is the most common among all genetically diagnosable nemaline myopathies in our center, although mildly increased lipid droplets are also constantly observed features.