The Research Of A Familial Paroxysmal Kinesigenic Dyskinesia Family

BackgroundParoxysmal kinesigenic dyskinesia(Paroxysmal kinesigenic dyskinesia,PKD)is a clinically rare nervous system disease,and it is mostly seen in the childhood period and adolescence.The clinical manifestation of PKD is the temporary and repeated attack of dyskinesia induced by sudden exercise and rage,which typically includes choreic movement,athetosis and dystonia.The attack may last from about a few seconds to a few minutes.Patients are normal during diapause,but it may attack over ten times every day.For those showing serious symptoms,the number may be over a hundred.According to etiology,PKD can be divided into the primary disease and secondary disease.Based on the family history of primary paroxysmal exercise-induced dyskinesia patients,it can be further divided into the sporadic disease and familial disease.The concept of paroxysmal kinesigenic dyskinesia familiar to us today was proposed by Demirkiran and Jankovic in 1995,but specific etiological factors and pathogenesis of the disease are not completely clear with the existence of many theories.However,no consensus has been reached among those theories,so further textual researches are required.As molecular genetics develops,more and more scholars reckon that PKD is related to genetic factors.With the continuous proceeding of researches,Chinese scholars initially reported in 2011 that(Proline-rich transmemebrane protein2,PRRT2)gene was related to paroxysmal exercise-induced dyskinesia as the pathogenic gene of PKD,which allows us to have ground-breaking understanding of PKD.The discovery of PRRT2 gene as the pathogenic gene of familial PKD can help to provide new experience and evidence for the diagnosis of the molecular level of such diseases,so as to improve the diagnostic rate.Furthermore,for the next generation of patients,gene transmission can be well prevented via prenatal genetic testing.ObjectiveThe clinical phenotype research and gene testing for a PKD family is carried out,so as to achieve in-depth understanding of the disease and detect the gene mutation site of the family.In this way,it is expected to obtain new mutation sites and provide new experience and evidence for the molecular level diagnosis of such diseases.Meanwhile,explore the pathogenesis of PKD.Methods1.Collect materials Clinical materials of a patient diagnosed with paroxysmal kinesigenic dyskinesia by the neurology department of the First Affiliated Hospital of Zhengzhou University and his family members are collected by the research.Clinical symptoms of the patient are analyzed.With the approval of the consent by the patient and his families as well as the ethics committee of the First Affiliated Hospital of Zhengzhou University,the blood of the patient and his families is drawn for gene testing analysis.2.Genomic DNA extraction Relevant liquid phase capture kit is utilized to extract genomic DNA.3.Preparation of the sample library Quality test of the library is conducted along with the capture experiment for the target area.4.Analysis of gene mutation High-throughput sequencing and analysis is conducted for the capture sequence on the sequencer.Result1.The family has the disease for three consecutive generations,the onset age of I1,II3,II6,III4,III6 were 26,17,16,12,10 years,the onset age is smaller and smaller with aggravation.2.Similar clinical manifestation is seen on the proband,his grandfather,father,aunt and cousin,showing limb dystonia after sudden movement.However,different clinical phenotypes about precipitating factors and specific symptoms are shown on patients in the family.The aunt of the proband belongs to II6,and rage or tension is an incentive for her.The cousin of the proband belongs to III6,and his disease may be induced when experiencing changes.The grandfather of the proband belongs to I1,and he would be unable to talk or be tongue-tied when attacked by the disease.The aunt of the proband belongs to II6,and her head and neck muscles may be accompanied by spasmodic torticollis when attacked by the disease.3.The result is obtained through the gene sequencing and analysis of the peripheral blood of 4 patients in the family: loss of the overall heterozygosis of PRRT2 gene.4.For PKD patients taking low-dose antiepileptic drugs,their symptoms can be well controlled.Conclusion1.The genetic early phenomenon exists in the familial paroxysmal kinesigenic dyskinesia,so there is a possibility of clinical phenotype heterogeneity or defective explicit by the disease.2.The PRRT2 gene is a causative gene of familial paroxysmal kinesigenic dyskinesia,and the loss of PRRT2 gene heterozygosis can lead to the familial paroxysmal kinesigenic dyskinesia.3.For patients showing PKD clinical symptoms,genetic testing can be conducted to confirm the diagnosis after excluding the possibility of similar diseases like epilepsy and secondary PKD.