Department of Pediatric, Tianjin Children's Hospital, Tianjin, 300134, China.
Graduate School, Tianjin Medical University, Tianjin, 300070, China.
Ital J Pediatr. 2020 Nov 4;46(1):166. doi: 10.1186/s13052-020-00925-1.
Spinal muscular atrophy (SMA) is an autosomal recessive hereditary disease associated with severe muscle atrophy and weakness in the limbs and trunk. The discovery of mutated genes is helpful in diagnosis and treatment for SMA.
Eighty-three whole blood samples were collected from 28 core families of clinically suspected SMA, and multiplex ligation probe amplification (MLPA) was performed. Afterwards, the complete gene sequence of SMN1 gene was detected. Furthermore, 20 SMA patients were selected from the 28 probands, and 5 non SMA children as controls. The Life Technologies SOLiD™ technology with mate-pair chemistry was utilized to conduct the whole exome high-throughput sequencing.
Twenty-two probands were SMA patients, 3 probands carriers, and 3 probands normal individuals. Moreover, 2 parents from 2 SMA families were with 3 SMN1 exon7 copies. Six SMN1 single nucleotide variants (SNVs) were identified in the 83 samples, and c.[84C > T], c.[271C > T], c.[-39A > G] and g.[70240639G > C] were novel. Compared with control group, 9102 mutation were selected out in SMA patients. SPTA1 mutation c.[-41_-40insCTCT], FUT5 SNV c.[1001A > G], and MCCC2 SNV c.[-117A > G] were the 3 most frequent mutations in SMA group (95, 85 and 75%, respectively).
We identified some mutations in both SMN1 and other genes, and c.[271C > T], c.[-41_-40insCTCT], c.[1001A > G] and c.[-117A > G] might be associated with the onset of SMA.
脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传性疾病，与四肢和躯干严重的肌肉萎缩和无力有关。突变基因的发现有助于 SMA 的诊断和治疗。
采集 28 个临床疑似 SMA 的核心家系的 83 例全血样本，进行多重连接探针扩增（MLPA），然后检测 SMN1 基因的完整基因序列。从 28 个先证者中选择 20 个 SMA 患者和 5 个非 SMA 儿童作为对照。利用 Life Technologies SOLiD™ 技术与 mate-pair 化学进行全外显子高通量测序。
22 个先证者为 SMA 患者，3 个先证者为携带者，3 个先证者为正常个体。此外，2 个 SMA 家系的 2 个父母均有 3 个 SMN1 外显子 7 个拷贝。在 83 个样本中鉴定出 6 个 SMN1 单核苷酸变异（SNV），c.[84C > T]、c.[271C > T]、c.[-39A > G]和 g.[70240639G > C]为新发现的变异。与对照组相比，在 SMA 患者中选择出 9102 个突变。SMA 组最常见的突变有 SPTA1 基因 c.[-41_-40insCTCT]、FUT5 基因 SNV c.[1001A > G]和 MCCC2 基因 SNV c.[-117A > G]，分别为 95%、85%和 75%。
我们在 SMN1 和其他基因中发现了一些突变，c.[271C > T]、c.[-41_-40insCTCT]、c.[1001A > G]和 c.[-117A > G]可能与 SMA 的发病有关。
