Abstract：
Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X-linked recessive allelic muscle diseases caused by dystrophin gene mutations. Eight hundred thirty-seven patients admitted between 1997 and 2022 were included in the study. Two hundred twenty patients were analyzed by multiplex PCR (mPCR) alone. Five hundred ninety-five patients were investigated by multiplex ligation-dependent probe amplification (MLPA), and 54 patients were examined by sequencing. Deletion was detected in 60% (132/220) of the cases in the mPCR group only and in 58.3% (347/595) of the cases with MLPA analysis. The rates of deletion and duplication were 87.7% and 12.3%, respectively, in the MLPA analysis. Single exon deletions were the most common mutation type. The introns 43-55 (81.8%) and exons 2-21 (13.1%) regions were detected as hot spots in deletions. It was determined that 89% of the mutations were suitable for exon skipping therapy. The reading frame rule did not hold in 7.6% of D/BMD cases (17/224). We detected twenty-five pathogenic/likely pathogenic variants in sequencing, five of which were novel variants. Nonsense mutation was the most common small mutation (44%). 21% of DMD patients were familial. We detected germline mosaicism in four families (4.3%) in the large rearrangement group and one gonosomal mosaicism in a family with a nonsense mutation. This is the largest study examining genotype and phenotype data in Turkish D/BMD families investigated by MLPA analysis. The reading frame hypothesis is not valid in all cases. Sharing the genotype and phenotype characteristics of these cases in the literature will shed light on the molecular structure of DMD and guide gene therapy research. In genetic counseling, carrier screening in the family and possible gonadal mosaicism should be emphasized.
摘要：
Duchenne型肌营养不良(DMD)和Becker型肌营养不良(BMD)是由肌营养不良蛋白基因突变引起的X连锁隐性等位基因肌肉疾病。该研究纳入了1997年至2022年期间收治的8137名患者。仅通过多重PCR（mPCR）分析了220名患者。通过多重连接依赖性探针扩增（MLPA）研究了595例患者，54例患者进行测序检查。仅在mPCR组中的60％（132/220）的病例和MLPA分析的58.3％（347/595）的病例中检测到缺失。缺失率和重复率分别为87.7%和12.3%,分别,在MLPA分析中。单外显子缺失是最常见的突变类型。内含子43-55(81.8%)和外显子2-21(13.1%)区域被检测为缺失中的热点。确定89%的突变适用于外显子跳跃疗法。阅读框架规则在7.6%的D/BMD病例中不成立(17/224)。我们在测序中检测到25种致病/可能的致病变体，其中五个是新颖的变体。无义突变是最常见的小突变(44%)。21%的DMD患者为家族性。我们在大型重排组中的四个家庭（4.3％）中检测到了种系镶嵌性，在一个无意义突变的家庭中检测到了一个性腺镶嵌性。这是通过MLPA分析调查土耳其D/BMD家族的基因型和表型数据的最大研究。阅读框假设并非在所有情况下都有效。在文献中分享这些病例的基因型和表型特征将揭示DMD的分子结构并指导基因治疗研究。在遗传咨询中，应强调家庭中的携带者筛查和可能的性腺镶嵌性。
