The Study Of Mutations In A Family Of Hereditary Spastic Paraplegia Based On The Next Generation Sequencing

Objective: The aim of this study was to investigate the clinical characteristics and analyze the spastin gene mutation in a family of hereditary spastic paraplegia with a thin corpus callosum(HSP-TCC).Methods: All the family members were examined through detailed clinical evaluations, auxiliary examinations and MRI(magnetic resonance imaging), et al. Then we selected four members from the HSP-TCC family as the tested samples. Firstly, we detected one of four members with the exon sequencing of the causative genes associated with HSP, then detected other samples with the whole exome sequencing(WES) and Sanger sequencing in order to find which gene mutation involved. Variations identified were compared with the results from the control subject and our bioinformatics searched in the dbSNP, 1000 Genomes, et al. Finally, we obtain a lot of SNPs, Indels(insertions/deletions) and unknowned gene loci.Results: Didn’t find abnormal spastin gene mutation what was cloned in one of samples by the exon sequencing of the causative genes associated with HSP, but remove most of hereditary diseases whose clinical manifestations were similar to the HSP’s. Then, with taking the whole exome sequencing and Sanger sequencing in other samples, we had found a large number of new SNPs and Indels, and screened two candidate genes which were possibly significant: NBPF1 and AHI1 gene mutations.Conelusion: This kindred has typical clinical manifestations of HSP. The pathogenesis has no association with the mutation of the exons of spastin gene. Besides the known SNPs(single nucleotide polymorphisms) and Indels already deposited in the databases, we did not find any spastin gene mutation in the family. The pathogenic gene was not currently known spastin gene, possibly was a new rare mutation what was not successfully cloned of HSP subtype now. It may be a new isofrom of HSP. By means of the gene sequencing, we found a lot of new SNPs and Indels, and screened two candidate genes which were possibly significant: NBPF1 and AHI1 gene. We established the detection process of SPG successfully what could be used for early screening, gene diagnosis of HSP patients, and provide a reliable basis for prenatal diagnosis. Among the sanger sequencing, the exon sequencing of gene panel and the whole exome sequencing, every one has its advantages and disadvantages. The correct selection of genetic testings, the rigorous sequencing process and complete information analysis method were necessary conditions to ensure the results are accurate.