背景:肌营养不良蛋白病是由肌营养不良蛋白(DMD)基因的致病变体引起的X连锁隐性疾病。在一个包括两个由于外显子45-47的DMD缺失而患有贝克尔肌营养不良症(BMD)的男孩的家庭中,母体携带者测试意外地发现了外显子45-47和49-51的双等位基因DMD缺失。
方法:患者在双等位基因DMD变异中的轻度表型促使进一步研究外显子49-51缺失,通过文献回顾和回顾性图表回顾在我们机构的综合神经肌肉中心评估和/或在我们的临床基因检测实验室诊断的患者。
结果:据我们所知,这只是第5例女性DMD双等位基因变异的确诊病例.在男性中,DMD外显子49-51缺失似乎导致轻度BMD表型,肌酸激酶水平低或正常.在我们的临床实验室中,在过去的十年中,这种缺失包括通过染色体微阵列(CMA)诊断为男性的19%(4/21)的肌营养不良蛋白病。大多数通过图表审查确定的人都是通过CMA诊断的,尽管微阵列是全基因组的,而不是DMD特异性的。这个案例引发了重要的遗传咨询问题。
结论:DMD外显子49-51缺失似乎导致可变的但通常是轻度的BMD表型。CMA相对频繁的检测表明它可能被诊断不足。
Dystrophinopathies are X-linked recessive conditions caused by pathogenic variants in the dystrophin (DMD) gene. In a family that included two boys with Becker muscular dystrophy (BMD) due to a DMD deletion of exons 45-47, maternal carrier testing unexpectedly identified biallelic DMD deletions of exons 45-47 and 49-51.
The patient\'s mild phenotype in the setting of biallelic DMD variants prompted further investigation of the exon 49-51 deletion in particular, via literature review and retrospective chart review of patients who have been evaluated in our institution\'s comprehensive neuromuscular center and/or diagnosed in our clinical genetic testing laboratory.
To our knowledge, this is only the fifth case of confirmed biallelic DMD variants in a female. In males, the DMD exon 49-51 deletion appears to result in a mild BMD phenotype with low or normal creatine kinase levels. This deletion comprised 19% (4/21) of dystrophinopathies diagnosed by chromosomal microarray (CMA) in males during the past ten years in our clinical laboratory. Most individuals identified by chart review were diagnosed through CMA, despite the fact that microarray was genome-wide and not DMD-specific. This case raised important genetic counseling issues.
The DMD exon 49-51 deletion appears to cause a variable but generally mild BMD phenotype. Its relatively frequent detection by CMA suggests it may be underdiagnosed.