Abstract：
5q-associated spinal muscular atrophy (SMA) is the most common autosomal recessive neurological disease. Depletion in functional SMN protein leads to dysfunction and irreversible degeneration of the motor neurons. Over 95 % of individuals with SMA have homozygous exon 7 deletions in the SMN1 gene. Most of the remaining 4-5 % are compound heterozygous for deletion and a disease-associated sequence variant in the non-deleted allele. Individuals with SMA due to bi-allelic SMN1 sequence variants have rarely been reported. Data regarding their clinical phenotype, disease progression, outcome and treatment response are sparse. This study describes six individuals from three families, all with homozygous sequence variants in SMN1, and four of whom received treatment with disease-modifying therapies. We also describe the challenges faced during the diagnostic process and intrafamilial phenotypic variability observed between siblings.
摘要：
5q相关脊髓性肌萎缩症（SMA）是最常见的常染色体隐性遗传性神经系统疾病。功能性SMN蛋白的耗尽导致运动神经元的功能障碍和不可逆的变性。超过95%的具有SMA的个体在SMN1基因中具有纯合外显子7缺失。剩余的4-5%中的大多数是用于缺失的复合杂合的,并且在未缺失的等位基因中是疾病相关序列变体。很少报道由于双等位基因SMN1序列变异而患有SMA的个体。有关其临床表型的数据，疾病进展,结果和治疗反应稀疏。这项研究描述了来自三个家庭的六个人，所有患者均在SMN1中具有纯合序列变异,其中4人接受了疾病改善疗法治疗.我们还描述了在诊断过程中面临的挑战以及兄弟姐妹之间观察到的家族内表型变异性。
