深内含子和RNA测序的整合增强了遗传上未解决的Pompe病例的分子诊断
Integration of deep intronic and RNA sequencing enhances molecular diagnosis in genetically unsolved Pompe cases.
摘要(中文译文)
我们描述了一种整合深内含子测序和RNA测序的诊断流程，用于解决遗传学上未明确的庞贝病病例。一名5岁女孩因肥厚型心肌病、肌无力、反复呼吸道感染、肌酸激酶水平升高以及α-葡萄糖苷酶活性降低而被转诊至代谢科。由两个不同遗传学实验室进行的庞贝病基因检测均未发现任何突变。两年后，该患者被转诊进行进一步基因检测。作为我们诊断流程中的第三步基因检测，在外显子测序和MLPA之后，进行了全基因测序检测，结果发现纯合NM_000152.5：c.1327-419 A > G变异。RNA测序证实存在外显子延伸，表明该新变异产生了一个新的供体剪接位点。最终，该患者获得了基因诊断并接受了适当治疗。本研究强调了在未明确庞贝病病例的分子诊断中，纳入深内含子测序和RNA测序作为必要后续步骤的重要性，并进一步揭示了该基因中的一个新致病性变异。
Abstract
We describe a diagnostic workflow integrating deep intronic and RNA sequencing to resolve genetically unsolved Pompe cases. A five-year-old girl with hypertrophic cardiomyopathy, muscle weakness, recurrent respiratory tract infections, elevated CK levels, and low alpha-glucosidase enzyme activity was referred to the metabolism department. Genetic tests for Pompe disease, conducted by two different genetic laboratories, failed to detect any mutation. Two years later, the patient was referred for further genetic testing. As the third-step genetic test in our diagnostic algorithm, following exonic sequencing and MLPA, the whole gene sequencing test was performed and revealed the homozygous NM_000152.5: c.1327-419 A > G variant. RNA sequencing confirmed exon extension, showing that this novel variant created a new donor splice site. Ultimately, the patient was genetically diagnosed and received appropriate treatment. This study highlights the importance of incorporating deep intronic and RNA sequencing is an essential subsequent step in the molecular diagnosis of unsolved Pompe cases, and it further reveals a novel pathogenic variant in the gene.
如何引用
AMA
Huseyin Onay, Deniz Kor, Fatma Derya Bulut, Ezgi Irmak Burgac, Bahadir Onay, Irem Kaplan, et al. Integration of deep intronic and RNA sequencing enhances molecular diagnosis in genetically unsolved Pompe cases.. Molecular genetics and metabolism reports. 2026; doi:10.1016/j.ymgmr.2026.101307.
APA
Huseyin Onay, Deniz Kor, Fatma Derya Bulut, Ezgi Irmak Burgac, Bahadir Onay, Irem Kaplan, et al (2026). Integration of deep intronic and RNA sequencing enhances molecular diagnosis in genetically unsolved Pompe cases.. Molecular genetics and metabolism reports. https://doi.org/10.1016/j.ymgmr.2026.101307
GB/T 7714
Huseyin Onay, Deniz Kor, Fatma Derya Bulut, Ezgi Irmak Burgac, Bahadir Onay, Irem Kaplan, et al. Integration of deep intronic and RNA sequencing enhances molecular diagnosis in genetically unsolved Pompe cases.[J]. Molecular genetics and metabolism reports, 2026 doi:10.1016/j.ymgmr.2026.101307.
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