Phenotype-genotype Study Of Chinese Patients With Duchenne/Becker Muscular Dystrophy

BackgrounBackground Duchenne/Becker muscular dystrophy (DMD/BMD) is a serious X-linkedneuromuscular disorder. It primarily involved the skeletal muscle, characterized by weakness andmuscle atrophy of hereditary muscle disease following a slow progressive increase of symmetry,may be associated with cognitive impairment at rest and myocardial damage. DMD seriouscondition in which a poor prognosis, usually died around the age of 20 due to respiratory failureor heart failure; BMD is a relatively slow progress, and the patients can still have the ability towalk after the first 15 to 20 years .Because the disease is currently no effective treatment, it isefficient and accurate detection of disease genes DMD, and the detection of carrieries, prenataldiagnosis and genetic counseling as the key to preventing this disease.Objective To establish molecular genetic methods for the diagnosis of DMD / BMD,and helpsome families for genetic counseling and prenatal diagnosisï¼›Analyzed the relationship betweengenotype and phenotype.Methods Collected and summarized the information of 100 DMD/BMD patients which werecollected in Peking University First Hospital, Some patients received muscle biopsy and routinepathological checks and immunohistochemistry staining was performed on biopsied musclespeciments with some antibodies. Genomic DNA was extracted using standard procedures fromthe peripheral blood leukocytes, and multiplex ligation-dependent probe amplification (MLPA)was applied to detect DMD gene to identify genetic mutation. These data were collected fromPeking University First Hospital and these works were all finished in pediatrics lab andneuropathologic lab of Peking University First Hospital.Results 1.Among 100 cases of clinical diagnosed DMD/BMD patients, exons deletion of DMDwas detected in 63 cases (63%),exons duplication in 9 (9%). Among 34 mothers with an affectedboy but without previous genetic conformation, 17 were confirmed to be carriers with genedeletion/duplication.Prenatal diagnosis was provided for one mother in her next pregnancydetecting a female carrier fetus.2. The data showers that frameshift rules can explain the relationship between DMDexon deletion/ duplication and the clinical severity, the rate is 77.78%(56/72)Conclusion 1. MLPA is a non-complex and quick diagnostic tool for DMD/BMD and its carriers,and also helpful in genetic counseling. 2. DMD gene deletions mainly occurs between exons 45-54, while duplicationsmostly at 5'-terminus.3.Mutation types of Chinese DMD/BMD patients conform the reading-frame rule...