PRRT2Gene Screening And Analysis Of Resting-state F-MRI In Paroxysmal Kinesigenic Dyskinesia

Paroxysmal dyskinesias (PD)are characterized by attacks of dyskinesia such as choreoathetosis, ballism, athetosis or dystonia triggered by defined stimuli. It can be divided in three distinct forms:Paroxysmal kinesigenic dyskinesias(PKD)is the most common type of PD.Characteristically, symptoms most commonly occur when a patient stands up quickly or is startled. Variations may present with chorea, athetosis, dystonia, ballism, or a combination of these hyperkinetic movement disorders. Symptoms usually manifest unilaterally, but may alternate or even be bilateral. Limbs are more commonly involved, but neck, face, and trunk may also be affected. PKD can be classified etiologically as primary (idiopathic or familial) or secondary according to the etiology. PKD has been shown to be inherited in an autosomal dominant fashion. The PRRT2gene on chromosome16was identified as the cause of the disease. This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. PRRT2gene is involved in signaling between nerve cells in the brain and helps control the release of neurotransmitters, which are chemicals that relay signals from one neuron to another. The mechanism of how PRRT2causes PKD still requires further investigation. The most common mutation type are c.649-650ins C p.Arg217Profs*8. Functional magnetic resonance imaging is a functional neuroimaging procedure using MRI technology that measures brain activity by detecting associated changes in blood flow. fMRI has several significant advantages:It is non-invasive and doesn’t involve radiation, making it safe for the subject. It has excellent spatial and good temporal resolution. Resting-state fMRI has revealed a number of networks which are consistently found in healthy subjects, different stages of consciousness and across species, and represent specific patterns of synchronous activity.In the present study, retrospective analysis of clinical features and PRRT2gene sequencing in patients with PKD were made to find out the characteristics of PKD, the spectrum of PRRT2gene mutations Our study may contribute to futher diagnosis of PKD,and understanding of the complicated relationship between genotype and phenotype in PRRT2gene.At the same time,29patients with PKD were included and interictal brain fMRI was performed in the patients and in the normal controls.Voxel-based analysis was used to characterize the alteration of amplitude of low frequency fluctuation (ALFF) and ReHo maps.It is contribute to understand the mechanism of PKD.Part Ⅰ:Clinical characteristics of PKD and PRRT2gene mutation testing.Objective:Retrospective analysis the clinical data of PKD families and sporadic cases to further the understanding of this disease and improve the diagnostic accuracy.27of them had been taken gene mutation testing for understanding the if the PRRT2gene mutations had existed. Methods:Collect the clinical, electrophysiological and imaging data of8propositus and64 sporadic cases.4propositus and23sporadic cases under DNA extraction for the PRRT2gene mutation testing.Results:Male/Female ratio was3.5:1. The average age of morbidity was12.93±3.96. Clinical symptoms most commonly occurred when a patient began to move quickly or is startled, with the abnormal motion in unilateral or bilateral limbs, however, face and trunk may also be affected. Most attack with aura may last a few seconds to tens of seconds, and may not exceed1minute. Treatment with antiepileptic drugs were effective. Exons gene mutation testing of PRRT2gene was found in4cases:c.981ATC>ATG p.327Ile>Met; c.649-650insC p.Arg217Profs*8; c.649CGA>TGA p.217Arg>Ter(end); c.5GCA>GTA p.2Ala>Val.there was no relationship between mutant type and clinical phenotype.Conclusions:1. PKD is one of the most common type of the paroxysmal dyskinesias. The typical symptoms of chorea, athetosis and dystonia are often occur when a patient stands up quickly or is startled.2. We first reported the mutation in noncoding region c.5GCA>GTA p.2Ala>Val. PRRT2gene mutation frequency in sporadic cases was about30%. And there may be other pathogenic factors that result in PKD. Gene mutations and clinical phenotype had no obvious correlation. Part II:Resting-state fMRI research in PKD patients. Objective:The purpose of this study is to localize cerebral functional abnormalities in idiopathic PKD with restingstate functional magnetic resonance imaging (fMRI). Voxel-based analysis was used to characterize the alteration of amplitude of low frequency fluctuation (ALFF) and ReHo maps.It is contribute to understand the mechanism of PKD.Methods:29cases of PKD patients and14normal controls were concluded. Interictal brain fMRI was performed in the patients and in the normal controls.resting MRI scans. The modes of the whole brain spontaneous activity were obtained by calculating ALFF and ReHo value.Results:Difference between the patient patterns and the control was analyzed with Student t-test. The whole brain analysis indicated that the patient group had significantly increased ALFF in the posterior cingulate cortex and premotor cortex than the normal control. Patients also had higher DMN than controls in the precuneus/posterior cingulate cortex,inferior parietal lobule and superior frontal gyrus. In the premotor cortex,the local consistency also significantly higher than the normal control. Conclusions:fMRI could be useful to evaluate PKD with negative conventional imaging. It was suggested that abnormal premotor cortex might be associated with the pathophysiology of idiopathic PKD.Premotor cortex may be a important node to understand the pathophysiology of PKD.The results Provide a region of interest for subsequent research. The interictal high excitability in PKD patients may be able to provide indicators for assessing patient’s condition.