Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy
Clinicogenetic lessons from 370 patients with autosomal recessive limb-girdle muscular dystrophy
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DOI：
10.1111/cge.13597
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发表时间：
2019-10-01
影响因子：
3.5
通讯作者：
Saute, Jonas A.
中科院分区：
文献类型：
--
作者：
Winckler, Pablo B.;da Silva, Andre M. S.;Saute, Jonas A.
肢体带状肌营养不良(LGMD)是一组以近端肌肉无力为主要特征的遗传异质性疾病。我们的目标是研究巴西常染色体隐性遗传LGMD2/LGMD-R患者的流行病学、临床和分子生物学特征。在13个中心进行了一项多中心历史队列研究，其中回顾了2017年7月至2018年8月期间连续诊断为LGMD2/LGMD-R的连续家系的指示病例及其受影响亲属的数据。建立了LGMD2A/LGMD-R1-calain 3相关、LGMD2B/LGMD-R2-deferlin相关和肌糖症的主要障碍的生存曲线，并根据性别和基因估计进展情况。在370例(305个家系)LGMD2/LGMD-R患者中，最常见的亚型是LGMD2A/LGMD-R1-calain 3相关亚型和LGMD2B/LGMD-R2相关亚型，各占家系的30%左右。肉糖症是最常见的儿童期发病亚型，占家庭总数的21%。5%的家庭患有与LGMD2G/LGMD-R7相关的端粒素，这是一种全球范围内极其罕见的亚型。与男性相比，携带LGMD2B/LGMD-R2基因缺陷相关基因的女性患者发展为残疾的程度较轻，而携带截短基因变异的LGMD2A/LGMD-R1-calain 3相关患者的发病时间较早，进展为残疾的情况较不存在基因截短基因变异的患者更为严重。我们提供了巴西LGMD2/LGMD-R的重要流行病学数据，可能有助于鉴别诊断，更好的患者护理，并指导未来的合作临床试验和该领域的自然历史研究。
Limb-girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical and molecular data of patients with autosomal recessive LGMD2/LGMD-R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD-R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD-R1-calpain3-related, LGMD2B/LGMD-R2-dysferlin-related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD-R, most frequent subtypes were LGMD2A/LGMD-R1-calpain3-related and LGMD2B/LGMD-R2-dysferlin-related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood-onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD-R7-telethonin-related, an ultra-rare subtype worldwide. Females with LGMD2B/LGMD-R2-dysferlin-related had less severe progression to handicap than males and LGMD2A/LGMD-R1-calpain3-related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD-R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field.