MLPA-based genotype–phenotype analysis in 1053 Chinese patients with DMD/BMD

Abstract

Abstract Background Large-scale analysis of the transmission, mutation characteristics and the relationship between the reading frame and phenotype of the DMD gene has previously been performed in several countries, however, analogous studies have yet to be performed in Chinese populations. Methods Clinical data from 1053 Chinese patients with DMD/BMD were collected, and the DMD gene was tested by MLPA in all patients and 400 proband mothers. In 20 patients with negative MLPA, sequencing was also performed. Results We found that 27.50% of cases had a family medical history of DMD/BMD, and large rearrangements were identified in 70.56% of the probands, of which 59.35% and 11.21% were deletions or duplications, respectively. The carrier status of the mothers in the study was determined to be 50.75%, and it was established that the DMD mutation was inherited from the mother in 51.72% of the probands. Exons 45–54 and 3–22 were the most frequently deleted regions, and exons 3–11 and 21–37 were the most prevalently duplicated regions of the gene. Breakpoints mainly occurred in introns 43–55 for deletion mutations and in introns 2 and 7 for duplication mutations. No breakpoints were found at the 5′ or 3′ end of introns 31, 35, 36, 40, 65, 68, and 74–78 in any of the deletion or duplication mutations. The reading frame rule held true for 86.4% of the DMD patients and 74.55% of the BMD patients. Conclusion It is essential to increase physicians’ understanding of DMD/BMD, to promote scientific information, and to increase awareness in regards to genetic counseling and prenatal diagnosis in pedigrees with a family history of the disease, particularly in families with small DMD lesions in China. In addition, such a large-scale analysis will prove to be instructive for leading translational studies between basic science and clinical medicine.