| Objective Paroxysmal kinesigenic dyskinesia(PKD) is a rare neurologic inherited disease. Recently, the PRRT2 gene on chromosome 16 was identified as the cause of the disease. In order to define the relationship between PRRT2 gene with PKD and influence of PRRT2 gene mutation to clinical phenotype.1. To learn PRRT2 gene bioinformatic information;2. To define the frequence of PRRT2 gene mutations in the recruit PKD patients and the information of PRRT2 gene mutation in the study;3. To discuss the influence of PRRT2 gene mutation to clinical phenotype in the recruit PKD patients.Methods1. We searched PRRT2 gene by biological network databases and made bioinformatic analysis.2. We collected 22 subjects, including 12 patients and 26 unaffected family members in 3 Northern Han Chinese pedigrees of PKD, 10 sporadic cases and 30 normal controls. All patients enrolled were examined by two neurological physicians. Then we recorded clinical data and extracted their peripheral blood.3. All exons of PRRT2 gene were sequenced by PCR Sanger sequencing to identify PRRT2 mutations. These PRRT2 gene mutations were tested in normal controls.4. Predict of 2-D protein structure was conducted by SWISS-MODEL.5. These patients enrolled in the study were follow-up for half a year to observe the effect of antiepileptic drug therapy, Clinical characteristics were compared between patients with PRRT2 gene mutations with patients without PRRT2 gene mutations by using SPSS 17.0 sofeware.Results1. PRRT2 gene consists of 4 exons, encoding 341 amino acids, and the protein is predicted to find two transmembrane domains, involving amino acids 269~289 and 318~338. Coding region of PRRT2 gene have 42 non-synonymous SNPs and 19 synonymous SNPs.2. We found the 412 C>G(Pro138Ala)mutation in PRRT2 exon 2 that resulted in an proine / alanine transition at codon 138 in 6 familial PKD patients and 3 sporadic PKD patients; the 917 C>A(Ala306Asp) mutation in PRRT2 exon 3 was found in 6 familial PKD patients and 2 sporadic PKD patients, resulting in an alanine/aspartic acid transition at codon 306. But the two gene mutations did not been found in all normal controls.3. The 2-D protein structure prediction showed that the 917 C>A(Ala306Asp) mutation in PRRT2 gene can’t chang 2-D protein structure.4. 22 PKD patients who were enrolled in the study were divided into patients with PRRT2 gene mutation and patients without gene PRRT2 mutations. The study revealed that patients who carried PRRT2 gene mutation have earlier onset age(average age: 10.31 vs 16.44, P = 0.027). Morover, Clinical symptoms is more symmetric and frequent(P = 0.007, P = 0.027); In terms of theonset of aura, there was no statistical significance in both groups(P = 0.054). After 6 months follow-up finding: carbamazepine treatment was competely effective for patients with PRRT2 gene mutations(11/11), but it was partially effective for patients without PRRT2 gene mutations(4/9).Conclusions1. The frequence of PRRT2 gene mutation is relatively high. Two missense mutation of PRRT2 gene are detected in the patients. So these 412 C>G(Pro138Ala) and 917 C>A(Ala306Asp) mutation may be the cause of PKD.2. Patients who carried PRRT2 gene mutations have earlier onset age comparing to patients who did not carry PRRT2 gene mutations, the onset of symptoms more symmetrical and frequent. At the same time, the study shows that patients who carried PRRT2 gene mutation to antiepileptic drug therapy is more effective, so it is possible that detecting PRRT2 gene to the clinical treatment of patients with PKD has potential significance.3. Genetic anticipation phenomenon may exist in Han Chinese pedigrees of PKD. |
