Genetic Characteristic And Gene Mutation Detection In One Benign Adult Familial Myoclonic Epilepsy Disease

Benign adult familial myoclonic epilepsy (BAFME), is an autosomal dominant,idiopathic epileptic syndrome, characterized by adult-onset tremulous fingermovement, myoclonus, epileptic seizures, and non-progressive course. Up to now, theworld there are about100family in Japan, Italy, the Netherlands, France, Turkey andChina were successively found and reported.But the disease has not yet beenincorporated into the2001international epilepsy syndrome classification ofantiepileptic alliance.The disease early reports are from Japan, the Japanese scholar Wakeno in1975reported a familial tremor and epilepsy as the ancestry of the performance, and thenhave reported more like family, and the electrophysiological study to determine itstremors are derived from the cerebral cortex, and all is autosomal dominantinheritance.In1991, Yasuda reported in two pedigrees, on the basis of this diseasewere summarized with a benign course and the characteristics of autosomal dominantinheritance, for the first time put forward the concept of benign familial myoclonicseizures in adults. In1999, Mikami using linkage analysis method to a3generation of27people suffering from the disease of the disease-causing gene location in8q23.3-24.1, to found the first gene loci of the disease.In2003, Strianon on an ItalianBAFME family genetic linkage analysis found that the gene loci on2p11-q12.2,which illustrates the genetic heterogeneity of the disease; In China in2006, deng feiyan, analized a BFAME pedigree, and found the pathogenic gene location to10p15;In2010, Depienne found a French FCMTE family pathogenic gene mapping in5p15.31-p15. In2012, Yeetong found a Thai BAFME pedigree pathogenic genelocation in3q26.32-3q28. So far, the gene of this disease has not been clone. Only Japanese scholarsAtsushi, In2003put forward CSMD3as the candidate genes that cause BFAME.CSMD3is a giant gene of1.2Mb consisting of73exons, it encodes a transmembraneprotein of CUB and sushi multiple domains and it is expressed mainly in fetal andadult brains, suggesting a good candidate for the pathogenic gene for the benign adultfamilial myoclonic epilepsy which has been mapped to8q23.3-q24.1.Since1991, Yasuda first puts forward the concept of BAFME, the research forBAFME only20years, however, most of them are reported cases, only a handful ofgenetics research reports, although made some research achievements, but it is lack ofsystem of pathogenic gene research report. Especially in our country, the study ofBAFME family reported is less, the big family is more rare. We have a big population,there are mang person have this disease, but our BAFME gene mutationcharacteristics is also not clear, so the Chinese BAFME genealogy research has greatsignificance. And actively carry out clinical and molecular genetics of this research ishelpful to improve clinicians understanding of the disease, to understanding themolecular pathogenesis of this disease and other idiopathic epilepsy. And provide thebasis for the disease diagnosis, treatment and genetic counseling.The research survey from a family in shenyang, liaoning province, afterinvestigation and analysis, diagnosed with BAFME. Communication with familymembers in details about the purpose and significance of the experimental studies,after signing of the informed consent, begin comprehensive genetic investigation,detailed medical history collection, auxiliary examination and collecting peripheralblood.The family comprised43individuals across four generations. Nine of thefamily members were affected(male2,femal7), with males and females affectedequally. This was consistent with autosomal dominant inheritance. Patients with onsetage at about30~40years old, a benign course.All patients with the similar clinicalmanifestations, distal limbs tremor as starting a symptom more, then, or a few yearslater attacks of systemic rigidity-clonus. Taking antiepileptic drugs can relieve symptoms effectively, beta blockers or drinking is invalid. The family has a cleargenetic relationship, is an autosomal dominant BAFME pedigree.Collecting peripheral blood of family members and some spouses, extract theleukocyte DNA for disease gene location. Ideas for the first experiment using PCRand PCR-DNA sequencing method to scan BAFME CSMD3gene mutation. If theresult is negative, then use the STR fluorescent marker gene linkage analysis toanalysis the BAFME gene which is known, attempt to mapping the disease gene to achromosomal region; if the current loci are all negative results, we use the wholegenome scan method to location disease gene. After orientation to the specificchromosomal region, select the gene near the loci which associated with epilepsy, toscan whether mutations exist in this familial BAFME, and to locate the specific genemutations in this BAFME family.First of all, the application of PCR product sequencing analysis propositus theCSMD3gene73exon of the PCR amplification product sequencing, the sequencingresults comparing with human GenBank CSMD3gDNA sequences, and found noDNA sequence variations, neither found polymorphic nor mutations associated withthe disease, suggests that his department does not exist CSMD3gene mutations.Thelinkage analysis excluded linkage to the chromosome region8q23.3-q24.1,2p11.1-q12.2,3q26.32-3q28,10p15, so we consider the causative genes for this family arenot in the above four chromosome region. And we selected four STR markers for5p15.31-p15, the linkage analysis results show that it is neither affirmation nornegation located in the region, and then, in order to find the clear results, we add eightSTR loci, the linkage analysis data showed that the LOD score was2.80for D5S486at no recombination. This suggested linkage to5p15.31-p15.1.This study suggeststhat the causative gene responsible for BAFME in the Chinese pedigree may belocated on chromosome5p15.31-p15.1.This experimental study learn the clinical feature, genetic characteristics andcausative gene loci of BAFME.The study provides experience for BAFME research, also gives the genetic studies of the disease a train of thought, and it is the first timeto report that the causative gene responsible for BAFME in the Chinese pedigreelocated on chromosome5p15.31-p15.1.