Prevalence and disease progression of genetically-confirmed facioscapulohumeral muscular dystrophy type 1 (FSHD1) in China between 2001 and 2020: a nationwide population-based study.
Prevalence and disease progression of genetically-confirmed facioscapulohumeral muscular dystrophy type 1 (FSHD1) in China between 2001 and 2020: a nationwide population-based study.
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2001年至2020年中国基因确诊1型面肩肱型肌营养不良症（FSHD1）的患病率和疾病进展：一项全国性人群研究
DOI：
10.1016/j.lanwpc.2021.100323
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Wang N
中科院分区：
文献类型：
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作者：
Wang Z;Qiu L;Lin M;Chen L;Zheng F;Lin L;Lin F;Ye Z;Lin X;He J;Wang L;Lin X;He Q;Chen W;Lin Y;Fu Y;Wang N
1型面肩肱型肌营养不良症（FSHD 1）是一种罕见的疾病，由于其异质性表现和复杂的分子遗传学基础，常常被漏诊，导致缺乏基于人群的流行病学数据，特别是患病率和疾病进展。福建省神经医学中心（FNMC）是中国临床遗传性FSHD的诊断中心，也是唯一一家采用脉冲场凝胶电泳（PFGE）为基础的Southern印迹进行所有FSHD 1基因检测的中心。使用分布在中国所有六个空间区域的三个来源获得关于FSHD 1事件的信息，即FNMC、遗传和肌病组（中华医学会神经病学分会）和“FSHD-中国”（FSHD患者支持的组织）。在2001-2020年期间，所有来自中国的基因确认的FSHD 1都在FNMC注册。在20年期间进行随访，以获得疾病进展的数据，主要描述为独立的amplitude损失。在纳入分析的1，744项FSHD 1基因检测（总检测数量为1，802）中，来自620个家庭的997名（57.2%）患者被诊断患有FSHD 1。2001-2020年，中国经基因确认的FSHD 1的估计患病率为0.75/百万（95%置信区间[CI]，0.70-0.79），其中男性为0.78（95% CI，0.72-0.85），女性为0.71（95% CI，0.65-0.78）。估计患病率从2001-2015年的0.22（95%CI，0.19-0.26）/百万增加到2016-2020年的0.53（95%CI，0.49-0.57）/百万（p < 0.001）。福建省2001-2020年、2001-2015年和2016-2020年的患病率分别为7.10/100万、4.66/100万和2.44/100万。在总共997例患者中的861例症状性加无症状患者中，首次肌无力的中位发病年龄为16岁（范围1-81）;收缩的D4 Z4重复序列的中位数量为5个单位（范围1-9）; 4 qA等位基因特异性甲基化水平的中位值为41%（范围14%-69%）。在2001-2020年随访的977例症状性患者中，117例患者（12.0%）失去了独立的Ampere。从首次出现肌无力到出现独立性肌无力丧失的预期持续时间为40年。与未丧失独立Ambassador的组相比，丧失独立Ambassador的组收缩的D4 Z4重复次数较少（p <0.001），首次肌无力的发病年龄较早（p < 0.001）。我们的研究捕获了全球最大的经基因确认的FSHD 1人群，计算出2001年至2020年中国的患病率为每百万人0.75人。大约12.0%的FSHD 1的症状性加无症状性患者将在首次肌无力发作后40年内失去独立的肌无力。这项工作得到了赠款（U2005201，81870902，N.W.）和（81974193，81671237，Z.Q.W.）国家自然科学基金项目;福建省科技创新联合基金项目（2018 Y 9082）（西北），福建省临床重点学科建设项目（西北）。
Facioscapulohumeral muscular dystrophy type 1 (FSHD1) is a rare disease, which is often underdiagnosed due to its heterogeneous presentations and complex molecular genetic basis, leading to a lack of population-based epidemiology data, especially of prevalence and disease progression. Fujian Neuromedical Centre (FNMC) is a diagnosis centre for clinical-genetic FSHD in China, and the only one employing pulsed-field gel electrophoresis (PFGE)-based Southern blotting for all FSHD1 genetic tests. Three sources distributed across all six spatial zones in China, were used to obtain information regarding FSHD1 events, namely, FNMC, Genetic and Myopathy Group (branches of the Neurology Society of the Chinese Medical Association), and “FSHD-China” (an organization supported by FSHD patients). During 2001-2020, all genetically-confirmed FSHD1 from China were registered in FNMC. Follow-up was conducted in the 20-year period to obtain data on disease progression, which was mainly described in terms of independent ambulation loss. Of the 1,744 FSHD1 genetic tests (total test number 1,802) included in the analysis, 997 (57.2%) patients from 620 families were diagnosed with FSHD1. The estimated prevalence of genetically-confirmed FSHD1 in China is 0.75 per million (95% confidence interval [CI], 0.70-0.79) during 2001-2020, with 0.78 (95% CI, 0.72-0.85) in males and 0.71 (95% CI, 0.65-0.78) in females. The estimated prevalence increased from 0.22 (95% CI, 0.19-0.26) per million in 2001-2015 to 0.53 (95% CI, 0.49-0.57) per million in 2016-2020 (p < 0.001). The prevalence in Fujian province was 7.10 per million, 4.66 per million, and 2.44 per million, during 2001-2020, 2001-2015, and 2016-2020, respectively. Among the 861 symptomatic plus asymptomatic patients of the total 997 patients, the median onset age at first-ever muscle weakness was 16 years of age (range 1-81); the median number of contracted D4Z4 repeats was 5 units (range 1-9); the median 4qA-allele-specific methylation level was 41% (range 14%-69%). Of the 977 symptomatic patients followed-up during 2001-2020, 117 patients (12.0%) lost independent ambulation. The expected duration from onset of first-ever muscle weakness to onset of independent ambulation loss was 40 years. The group with loss of independent ambulation had a smaller number of contracted D4Z4 repeats (p < 0.001) and had an earlier onset age of first-ever muscle weakness (p < 0.001) compared to the group without loss of independent ambulation. Our research captures the largest genetically-confirmed FSHD1 population worldwide, to calculate its prevalence of 0.75 per million in China from 2001 to 2020. Approximately 12.0% of symptomatic plus asymptomatic patients of FSHD1 will lose independent ambulation in 40 years from onset of first-ever muscle weakness. This work has been supported by the grants (U2005201, 81870902, N.W.) and (81974193, 81671237, Z.Q.W.) from the National Natural Science Foundation of China; Joint Funds for the Innovation of Science and Technology of Fujian Province (2018Y9082) (N.W.), and the Key Clinical Specialty Discipline Construction Program of Fujian (N.W.).