| Title | Neutral lipid storage disease with myopathy in China: a large multicentric cohort study |
| Authors | Zhang, Wei Wen, Bing Lu, Jun Zhao, Yawen Hong, Daojun Zhao, Zhe Zhang, Cheng Luo, Yuebei Qi, Xueliang Zhang, Yingshuang Song, Xueqin Zhao, Yuying Zhao, Chongbo Hu, Jing Yang, Huan Wang, Zhaoxia Yan, Chuanzhu Yuan, Yun |
| Affiliation | Peking Univ, Hosp 1, Dept Neurol, 8 Xishiku St, Beijing 100034, Peoples R China Shandong Univ, Qilu Hosp, Dept Neurol, 107 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai, Peoples R China Peking Univ Peoples Hosp, Dept Neurol, Beijing, Peoples R China Hebei Med Univ, Hosp 3, Dept Neurol, Shijiazhuang, Hebei, Peoples R China Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou, Guangdong, Peoples R China Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha, Hunan, Peoples R China Nanchang Univ, Affiliated Hosp 2, Dept Neurol, Nanchang, Jiangxi, Peoples R China Peking Univ, Hosp 3, Dept Neurol, Beijing, Peoples R China Hebei Med Univ, Hosp 2, Dept Neurol, Shijiazhuang, Hebei, Peoples R China |
| Keywords | Neutral lipid storage disease with myopathy Patatin-like phospholipase domain-containing 2 Rimmed vacuole Skeletal myopathy Cardiomyopathy |
| Issue Date | 2019 |
| Publisher | ORPHANET JOURNAL OF RARE DISEASES |
| Abstract | Background Neutral lipid storage disease with myopathy (NLSDM) is a rare clinical heterogeneous disorder caused by mutations in the patatin-like phospholipase domain-containing 2 (PNPLA2) gene. NLSDM usually presents skeletal myopathy, cardiomyopathy and the multiple organs dysfunction. Around 50 cases of NLSDM have been described worldwide, whereas the comprehensive understanding of this disease are still limited. We therefore recruit NLSDM patients from 10 centers across China, summarize the clinical, muscle imaging, pathological and genetic features, and analyze the genotype-phenotype relationship. Results A total of 45 NLSDM patients (18 men and 27 women) were recruited from 40 unrelated families. Thirteen patients were born from consanguineous parents. The phenotypes were classified as asymptomatic hyperCKemia (2/45), pure skeletal myopathy (18/45), pure cardiomyopathy (4/45), and the combination of skeletal myopathy and cardiomyopathy (21/45). Right upper limb weakness was the early and prominent feature in 61.5% of patients. On muscle MRI, the long head of the biceps femoris, semimembranosus and adductor magnus on thighs, the soleus and medial head of the gastrocnemius on lower legs showed the most severe fatty infiltration. Thirty-three families were carrying homozygous mutations, while seven families were carrying compound heterozygous mutations. A total of 23 mutations were identified including 11 (47.8%) point mutations, eight (34.8%) deletions and four (17.4%) insertions. c.757 + 1G > T, c.245G > A and c.187 + 1G > A were the three most frequent mutations. Among four groups of phenotypes, significant differences were shown in disease onset (< 20 years versus >= 20 years old, p = 0.003) and muscle pathology (with rimmed vacuoles versus without rimmed vacuoles, p = 0.001). PNPLA2 mutational type or functional defects did not show great impact on phenotypes. Conclusion We outline the clinical and genetic spectrum in a large cohort of NLSDM patients. Selective muscle fatty infiltration on posterior compartment of legs are characteristic of NLSDM. Chinese patients present with distinctive and relative hotspot PNPLA2 mutations. The disease onset age and pathological appearance of rimmed vacuoles are proved to be related with the clinical manifestations. The phenotypes are not strongly influenced by genetic defects, suggesting the multiple environmental risk factors in the development of NLSDM. |
| URI | http://hdl.handle.net/20.500.11897/553293 |
| DOI | 10.1186/s13023-019-1209-z |
| Indexed | SCI(E) EI |
| Appears in Collections: | 第一医院 人民医院 第三医院 |
