Clinical,Pathological And Molecular Biological Study Of Dysferlinopathy

Objective: Comprehensing the characteristics of clinical,pathological and genetic mutation to improve the diagnosis of dysferlinopathy and avoid misdiagnosis.Methods: In this study,a total of 28 cases with pathological diagnosis of dysferlinopathy were included in the second hospital of Hebei medical university from January 2014 to January 2017.We collected the clinical data of each patient and performed the muscle biopsies and genetic testing.Results:1.The result of genetic testing and genetic diagnosisIn this study,we performed the genetic testing of 28 patients with dysferlinopathy and 5 families.All of 28 patients was detected mutations,including 16 genes with 82 mutations and 32 novel mutations.According to the genetic test results,15 cases(53.57%)were confirmed,including 13 cases of dysferlinopathy and 2 cases of LGMD2 A.There were still 13 cases(46.43%)of undiagonsed genes.Combining with clinical and pathological diagnosis,we diagnosed 1 case of dysferlinopathy,1 case of LGMD2 A and 1 case of Becker muscular dystrophy.However,10 cases were still not clear based on the clinical,pathological and genetic testing results.2.Clinical data,pathological results,and DYSF gene mutations of patients diagnosed with dysferlinopathy.There were 14 patients comprehensively diagnosed as dysferlinopathy with an occult onset based on clinical,pathological and genetic test.The duration of disease was from 1 to 30 years.The age of onset was from 8 to 40 years,with an average of 25.23±8.358.Two of them had postive family history.The intinal sympotms were really different from each other.There were 7 cases of LGMD2 B type;3 cases of patients with "asymptomatic hypercalcemia";2 cases with "exercise intolerance";1 case with MM type and 1 case with proximal-distal type.A total of 12 patients performed creatinase kinase(2124U/L~12000U/L),with an average of 5874.19 + 2749.27U/L.Electrophysiological examination of 9 cases showed typical myogenic damages but 1 case was neurogenic lesion and 1 case showed roughly normal.1 case was approximately normal and 13 cases showed muscular dystrophy on muscular pathology.All of the 14 cases detected DYSF mutations in 26 sites and 10 novel mutations.Five family genetic testing results were consistent with autosomal recessive inheritance.3.Diagnosis and treatment of dysferlinopathy.8 of the 14 dysferlinopathy patients were misdiagnosed as inflammatory myopathy with a 57.14% clinical misdiagnosis rate,all of which were treated with methylprednisolone but didn’t have any obvious curative effect.Complete reduction of dysferlin protein after muscle biospy,and was accurate diagnosed as dysferlinopathy combining with DYSF gene mutation in gene detection.Conclusions:1.The onset of dysferlinopathy is in early adolescent or adult.The most common type is LGMD2 B diffcult in squating from chairs and climbing stairs independently.The serum creatinase kinase increases significantly in early asymptomatic stage.EMG shows typical myogenic damages.The main muscle pathology features of dysferlinopathy are muscular dystrophy.2.The immunohistochemical staining of dysferlin protein is completely absence or reduce,which can be used as the preferred method for clinical screening.But detecting the pathogenic DYSF gene mutation is the gold standard for the diagnosis of dysferlinopathy.3.There are a large number of novel mutations but no hotspots of DYSF.The genetic testing can detect other muscular dystrophy with secondary dysferlin proteins reduce.4.The clinical misdiagnosis of dysferlinopathy is really common.Clinical manifestation combining with muscle pathology and genetic testing can impr-ove the accurate diagnosis of dysferlinopathy.