Abstract：
Dysferlinopathies are a group of limb-girdle muscular dystrophies causing significant disability in the young population. There is a need for studies on large cohorts to describe the clinical, genotypic and natural history in our subcontinent. To describe and correlate the clinical, genetic profile and natural history of genetically confirmed dysferlinopathies. We analysed a retrospective cohort of patients with dysferlinopathy from a single quaternary care centre in India. A total of 124 patients with dysferlinopathy were included (40 females). Median age at onset and duration of illness were 21 years (range, 13-50) and 48 months (range, 8-288), respectively. The average follow-up period was 60 months (range, 12-288). Fifty-one percent had LGMD pattern of weakness at onset; 23.4% each had Miyoshi and proximo-distal type while isolated hyperCKemia was noted in 1.6%. About 60% were born to consanguineous parents and 26.6% had family history of similar illness. Twenty-three patients (18.6%) lost ambulation at follow-up; the median time to loss of independent ambulation was 120 months (range, 72-264). Single-nucleotide variants (SNVs) constituted 78.2% of patients; INDELs 14.5% and 7.3% had both SNVs and INDELs. Earlier age at onset was noted with SNVs. There was no correlation between the other clinical parameters and ambulatory status with the genotype. Thirty-seven (45.7%) novel pathogenic/likely pathogenic (P/LP) variants were identified out of a total of 81 variations. The c.3191G > A variant was the most recurrent mutation. Our cohort constitutes a clinically and genetically heterogeneous group of dysferlinopathies. There is no significant correlation between the clinico-genetic profile and the ambulatory status.
摘要：
异常疾病是一组肢体带肌营养不良，在年轻人群中引起严重的残疾。有必要对大型队列进行研究来描述临床，我们次大陆的基因型和自然史。为了描述和关联临床，遗传资料和自然历史的遗传证实的病。我们分析了来自印度一家第四系护理中心的糖尿病异常患者的回顾性队列。总共包括124例异常铁蛋白病患者（40例女性）。发病年龄和病程中位数为21岁(范围，13-50）和48个月（范围，8-288),分别。平均随访时间为60个月(范围,12-288）。51％的人在发病时具有LGMD无力模式；每个23.4％的人患有Miyoshi和近端远端型，而孤立的高CK血症占1.6％。大约60％的父母是近亲，26.6％的人有类似疾病的家族史。23例患者（18.6%）在随访时失去下床活动；失去独立下床活动的中位时间为120个月（范围，72-264）。单核苷酸变异（SNV）占78.2%的患者；14.5%和7.3%的INDEL同时具有SNV和INDEL。SNV注意到发病年龄较早。其他临床参数和动态状态与基因型之间没有相关性。在总共81种变异中，发现了37种（45.7％）新的致病性/可能的致病性（P/LP）变异。c.3191G>A变体是最反复发生的突变。我们的队列构成了一个临床和遗传异质性的异常疾病组。临床遗传特征与动态状态之间没有显着相关性。
