Variant analysis and therapeutic prospect for Chinese pedigrees affected with Duchenne/Becker muscular dystrophy from a single center over the past 15 years / 中华医学遗传学杂志

ABSTRACT

OBJECTIVE@#To summarize the result of genetic testing and therapeutic prospect of 2042 unrelated Chinese pedigrees affected with Duchenne/Becker muscular dystrophy (DMD/BMD) from a single center from 2005 to 2019.@*METHODS@#Peripheral blood samples of the pedigrees were collected for the detection of DMD gene variants with combined multiple ligation-dependent probe amplification (MLPA), next generation sequencing (NGS) and Sanger sequencing.@*RESULTS@#DMD and BMD have respectively accounted for 78.60% and 21.40% of the pedigrees, which included 33 female probands. Variants of the DMD gene were detected in 1986 pedigrees (97.26%). Large deletions, duplications and small-scale mutations have respectively accounted for 71.85%, 8.76% and 19.39%. Common deletions and duplications have included deletion of exons 45-50 and duplications of exon 2, while no hot spot was found with small-scale mutations. For 1595 pedigrees affected with DMD, 935 (58.62%) were hereditary and 660 (41.38%) were de novo in origin. 34.28% (700/2042) of the patients had symptoms which could be relieved by gene therapy.@*CONCLUSION@#This has been the largest single-center study of DMD pedigrees, which has attained definite diagnosis in 97.26% of the patients. The results have enabled genetic counseling and prenatal diagnosis for the affected families upon their subsequent pregnancies, enriched the spectrum of DMD gene variants, as well as facilitated study of the mechanism of DMD gene mutations and exploration of clinical treatment.