The Clinical,Pathological,and GNE Gene Mutations Analysis Of Distal Myopathy With Rimmed Vacuoles

Objective:In this research,we retrospectively reviewed the medical records of seven patients,including the clinical,pathologic,imaging and gene mutation examinations,and further analyzed the characteristics of gene mutation for better understanding of the hot genetic diseases in China.Considering the report about this disease in the world,we try to enrich the gene mutation spectrum of our nation and increase the clinicians' cognition of this disease.Materials and Method:Seven patients were diagnosed with DMRV in No.1 Hospital of Jilin University during the period from 2013 to 2016.We collected the clinical date,and suggested them to do the checkups of CK,muscle biopsy,electromyography,muscle MRI,and peripheral blood genetic testing.Result:1.Clinical featuresAll of the patients including two males and five females were at the age of 26-46 years old with the case history ranging from 2 years to decade.The onset age was 23-36 years old and the average onset age was 29.8 years old.Of all the patients,there were four lower-limbs-weakness cases,one upper-limbs-weakness case,and two upper & lower limbs weakness cases.All these cases were mainly distal limb weakness,including obviously involved lower limb tibialis muscle and visibly muscle atrophy of the legs and hands.Four patients were foot droop and "duck step".Among all these cases,quadriceps were not involved and weakened or disappeared tendon reflex were always found.2.Pathological featuresOpen muscle biopsy was carried out in all patients.Muscle biopsy study showed that rimmed vacuoles can be seen in Hematoxylin-eosin?H-E?staining,basophilic granules deposition can be found around these RVs.Besides,variation in fiber size was also observed.Small empty spaces were surrounded typically by tiny red granules in the cytoplasm of muscle fibers using modified Gomori trichrome?MGT?staining method.Inflammation cell infiltration was not seen.However,degeneration or necrotic muscle fibers were also found.3.Auxiliary examinationAccording to the CK examination results,we found the CK figure of four cases increased mildly with not more than 3 times,and EMG of them were myogenic damage.Additionally,three cases underwent muscle MRI examination,bilateral calves' MRI,suggesting that the tibial anterior muscle,tibial posterior muscle,extensor digitorum longus,fibular long muscle,fibular short muscle,gastrocnemius muscle of calves were involved obviously.Double thigh muscles' MRI indicated that medial and posterior group muscle were mainly involved.The muscle MRI revealed the main characteristics of muscle atrophy and steatosis.Apart from that,no obvious inflammatory exudation was observed while quadriceps femoris muscle were not involved.4.Gene mutation feathers?test results shown in Table 2?There were eight mutational sites found in total,including one of frameshift mutations and missense mutations of the others.Among them,five mutation,including p.D207 V,p.C44 S,p.G576 R,p.A669 P and p.D218 G have been reported,while three mutations?c.455₄56ins C,p.P421 L and p.A287T?were unknown.Conclusions:In this study,all the patients were sporadic in their early adult with no family medical history.The first symptoms were mostly distal weakness of the extremities or gait abnormalities and significant tibialis muscle involvement.The disease progressively increased,with CK mildly or moderately increased.The muscle biopsy pathology of them had confirmed the presence of RVs,variation in fiber size and deficiency of inflammatory cells.The muscle MRI examination of three patients showed that the calf muscle,medial and posterior group muscles' involvement were significant with muscle atrophy and steatosis while quadriceps was not involved.In conclusion,the cases were according with DMRV's clinical pathology diagnosis.Also,there were GNE site gene mutation in genetic analysis of all the patients,indicating the clear diagnosis of DMRV.Besides,the genetic testing results showed that there still existed unknown mutations,which could help to enrich the GNE gene spectrum of our nation.