脊髓性肌萎缩症（SMA）亚型在兄弟姐妹中的一致性：来自 Cure SMA 队列的研究结果。

BACKGROUND

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by homozygous survival of motor neuron 1 (SMN1) gene disruption. Despite a genetic etiology, little is known about subtype concordance among siblings.

OBJECTIVE

To investigate subtype concordance among siblings with SMA.

METHODS

Cure SMA maintains a database of newly diagnosed patients with SMA, which was utilized for this research.

RESULTS

Among 303 sibships identified between 1996 and 2016, 84.8% were subtype concordant. Of concordant sibships, subtype distribution was as follows: Type I, 54.5%; Type II, 31.9%; Type III, 13.2%; Type IV, 0.4%. Subtype and concordance/discordance association was significant (Fisher's exact test; p < 0.0001). Among discordant sibships (chi-square test, p < 0.0001), Types II/III (52.2%) and Types I/II (28.3%) were the most common pairs. No association was found between sibling sex and concordance. Our findings show that most siblings with SMA shared the same subtype concordance (most commonly Type I).

CONCLUSIONS

These data are valuable for understanding familial occurrence of SMA subtypes, enabling better individual treatment and management planning in view of new treatment options and newborn screening initiatives.

背景

脊髓性肌萎缩症（SMA）是一种常染色体隐性神经肌肉疾病，由运动神经元 1（SMN1）基因纯合缺失引起。尽管具有遗传病因，但对于 SMA 患者兄弟姐妹之间的亚型一致性知之甚少。

目的

调查 SMA 患者兄弟姐妹之间的亚型一致性。

方法

Cure SMA 维护着一个新诊断 SMA 患者的数据库，该数据库用于本研究。

结果

在 1996 年至 2016 年间确定的 303 个兄弟姐妹群体中，84.8%是亚型一致的。在一致的兄弟姐妹群体中，亚型分布如下：I 型，54.5%；II 型，31.9%；III 型，13.2%；IV 型，0.4%。亚型和一致性/不一致性的关联具有统计学意义（Fisher 确切检验；p<0.0001）。在不一致的兄弟姐妹群体中（卡方检验，p<0.0001），II/III 型（52.2%）和 I/II 型（28.3%）是最常见的组合。兄弟姐妹的性别与一致性之间没有关联。我们的发现表明，大多数 SMA 兄弟姐妹具有相同的亚型一致性（最常见的是 I 型）。