Discovery of specific mutations in spinal muscular atrophy patients by next-generation sequencing

Spinal muscular atrophy (SMA) is a type of autosomal recessive genetic disease, which seriously threatens the health and lives of children and adolescents. We attempted to find some genes and mutations related to the onset of SMA. Eighty-three whole-blood samples were collected from 28 core families, including 28 probands with clinically suspected SMA (20 SMA patients, 5 non-SMA children, and 3 patients with unknown etiology) and their parents. The multiplex ligation probe amplification (MLPA) was performed for preliminary diagnosis. The high-throughput sequencing technology was used to conduct the whole-exome sequencing analysis. We analyzed the mutations in adjacent genes ofSMN1gene and the unique mutations that only occurred in SMA patients. According to the MLPA results, 20 probands were regarded as experimental group and 5 non-SMA children as control group. A total of 10 mutations were identified in the adjacent genes ofSMN1gene.GUSBP1g.[69515863G>A],GUSBP1g.[69515870C>T], andSMA4g.[69515738C>A] were the top three most frequent sites.SMA4g.[69515726A>G] andOCLNc.[818G>T] have not been reported in the existing relevant researches. Seventeen point mutations in theDYNC1H1gene were only recognized in SMA children, and the top two most common mutations were c.[2869-34A>T] and c.[345-89A>G]; c.[7473+105C>T] was the splicing mutation that might change the mRNA splicing site. The mutations ofSMA4g.[69515726A>G],OCLNc.[818G>T],DYNC1H1c.[2869-34A>T],DYNC1H1c.[345-89A>G], andDYNC1H1c.[7473+105C>T] in the adjacent genes ofSMN1gene and other genes might be related to the onset of SMA.

Automated summary

This study identified mutations in adjacent genes of the SMN1 gene and other genes that may be associated with the onset of SMA through analysis of SMA family samples, including novel mutations not previously reported.