Clinical And Gene Mutation Analysis Of Duchenne Muscular Dystrophy In Children

Background and Objective:Pseudohypertrophc muscular dystrophy?PMD?is X-Linked recessive disorders,which is caused by defents in the dystrophingene.The PMD is divided into Duchenne muscular dystrophy?DMD?and Becker muscular dystrophy?BMD?.And the DMD,which got the character of the progressive and degenerative changes of muscle,is the most common type in the PMD.This disease has a poor prognosis,and the patient usually dies at 20 years old,because of the respiratory and/or heart failure.Compared with the DMD,the BMD is rare and has a relatively late onset,mild symptoms and slow clinical progress.At present,there is no effective cure for this disease.Therefore,the approaches,such as the detection of the DMD gene,the detection of the carriers who have the virulencegene,the prenatal diagnosis and genetic counseling,become the key to prevent the disease.Research objects and methods:We collected the clinical and laboratory data of 32 patients,who got the PMD.And we got their sequencing of the genomic DNA,which was extracted from the peripheral blood,by the means of the NGS?Next-generation sequencing?,MLPA?Multiplex ligation-dependent probe amplification?,Sanger?the first generation sequencing?.Then we use the methods of the disease database analysis to analyse and summarize the dystrophin gene mutation.Result:1.28 cases of DMD gene mutation were detected in 32 cases,the mutation rate was 87.5%.including 18 deletions?greater than or equal to an exon?account for 64.3%of the total mutation,3 duplications?greater than or equal to an exon?account for 10.7%,and 7 point mutations?25%?.2.The DMD exon deletion mutations mainly concentrated in exon 45?52,followed by exon 10-17.3.We detected three novel mutations,which were ChrX:31697619?c.365C>A,p.S122X?,ChrX:32361292?c.1674dupA,p.L559fs?,ChrX:31241169?c.9358₉359insA,P.Cys3120Leufs*12?,had not been reported in the literature.4.We had sequenced the genomic DNA the mother of the 18 cases of DMD gene mutation.Among these 18 families,we found 10 mothers carried the same heterozygous mutation as the patients.So the de novo rate?44.4%,8/18?.Conclusion:1.DMD gene mutations types were various,including exon deletion and/or duplication and point mutation.And the results of 3 new mutationsdiscoveryin DMD gene have enriched the mutation database of DMD gene.2.Economic and efficient genetic/prenatal diagnosis of DMD/BMD may be plausible by MLPA analysis,NGS and Sanger sequencing.It is meaningful that we can offer the prognostic judgment and genetic counseling to the pregnantwomen with a genetic history of the family,in order to prevent the DMD/BMD in advance.