Primary torsion dystonia (PTD) is a disease of the external vertebral body characterized by abnormal posture and movement, which is caused by uncoordinated or excessive contraction of the active muscle and the antagonist muscle. The pathogenesis of PTD is not completely understood. Over the last few decades, several novel disease associated genes (DYT1-27) have been identified in dystonic syndromes, but the underlying genetic diagnosis remains elusive in most patients [1].But,almost all primary dystonia have a genetic basis[2–3].
At present, the study of genetic diseases mainly lies in genes, and the method used in the study of genetic diseases is gene sequencing. With the development of whole genome sequencing, especially the cost of single human sequencing has dropped to ten thousand yuan, it has brought new opportunities for the study of genetic diseases.Many problems, such as too few members in the family, sporadic cases, heterogeneity of gene loci, penetrance, and too many candidate clones in the targeting region, have been resolved in the traditional cloning technology[4]. Genome wide sequencing has made up for the lack of disease related structural variations and non coding region variation in whole genome exon sequencing. Genome wide sequencing can detect genomic changes that can not be detected in other ways, such as noncoding mutations, including promoters, enhancers, introns, and noncoding RNA (including tiny RNA). Chromosomal rearrangements can be detected, including inversions, tandem repeats, and deletions. A large number of genetic differences can be found to achieve genetic evolution analysis and the importance of candidate gene prediction[5]. It involves many fields such as clinical medicine research, population genetics research, association analysis and evolutionary analysis. Compared with exome sequencing technology, the whole genome sequencing technology has been tested more widely, and the result analysis is more thorough to the study of genetic disease[6].
So far, the identification of PTD and genetic risk factors has proved to be a difficult task, and the introduction of the latest genome-wide sequencing technologies could drive progress in these areas[7]. As we can find its advantages which compare with HiSeq 2000 from the table 1. ANO3 encodes a homodimeric protein that is structurally related and encodes a Ca+ 2-activated chloride ion channel and a protein of a membrane phospholipid antibody having a different expression pattern. ANO3 consists of eight hydrophobic transmembrane helices that act as Ca+ 2 sensors for regulating calcium homeostasis [8]. The exact function of ANO3 is unclear, and recent experiments have shown that it does not act as a Ca+ 2 -activated chloride ion channel and may actually act as a Ca+ 2-dependent phospholipid fragment[9]. ANO3 appears to play a role in the regulation of neuronal excitability and is highly expressed in the striatum, hippocampus and cortex[10]. Mechanisms, pathogens in ANO3 may lead to striatal-neuronal excitability abnormalities, which manifested as uncontrolled dystonia movement. The expression level of ANO3 mRNA is the highest in striatum, 5.30 times that in frontal cortex and 70 times in cerebellum[11], and its abnormality can affect endoplasmic reticulum related calcium ion gated chloride channel, which leads to disease[12].
At present, the disease mainly rely on drugs and stereotactic surgical treatment, but the treatment is only symptomatic treatment, and there are many limitations, and the pathogenesis of dystonia is not completely clear; Therefore, it is necessary to screen new loci of DYT gene, discover new related genes, and study the mutant genes and related proteins.The research is based on whole genome sequencing technology of PTD patients to analyze the pathogenic genes and mutation sites in patients with primary dystonia, the relationship among genotype, clinical phenotype and prognosis. Detecting genetic mutations in genetic diseases and discovering new genes or mutations can help us to make the correct molecular diagnosis of the disease and to provide better genetic information.