Sun Gege, Huang Wei, Wang Li, Wu Jinlin, Zhao Ganye, Ren Huanan, Liu Lina, Kong Xiangdong
Genetics and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Genetics and Prenatal Diagnosis Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Clin Chim Acta. 2024 Jul 15;561:119774. doi: 10.1016/j.cca.2024.119774. Epub 2024 Jun 8.
Whole exome sequencing (WES) is becoming more widely used as a diagnostic tool in the field of medicine. In this article, we reported the diagnostic yield of WES and mitochondrial genome assessment in 2226 consecutive cases in a single clinical laboratory.
We retrospectively analyzed consecutive WES reports from 2226 patients with various genetic disorders. WES-process was focused exclusively on the probands and aimed at a higher diagnostic capacity. We determined the diagnostic rate of WES overall and by phenotypic category, mode of inheritance, mitochondrial genome variant, and copy number variants (CNVs).
Among the 2226 patients who had diagnostic WES proband-only, the overall diagnostic yield of WES was 34.59% (770/2226). The highest diagnostic yield was observed in autosomal dominant disorders, at 45.58% (351/770), followed by autosomal recessive at 31.95%(246/770), X-linked disorder at 9.61%(74/770), and mitochondrial diseases at a notably lower 0.65%(5/770). The 12.21% (94/770) diagnoses were based on a total of 94 copy number variants reported from WES data. CNVs in children accounted for 67.02% of the total CNVs. While majority of the molecular diagnoses were related to nuclear genes, the inclusion of mitochondrial genome sequencing in the WES test contributed to five diagnoses. all mitochondrial diseases were identified in adults.
The proband-only WES provided a definitive molecular diagnosis for 34.59% of a large cohort of patients while analysis of WES simultaneously analyzed the SNVs, exons, mitochondrial genome, and CNVs, thereby improving the diagnostic yield significantly compared to the single-detection WES method; and facilitating the identification of novel candidate genes.
全外显子组测序（WES）在医学领域作为一种诊断工具正得到越来越广泛的应用。在本文中，我们报告了在单一临床实验室对2226例连续病例进行WES及线粒体基因组评估的诊断率。
我们回顾性分析了2226例患有各种遗传疾病患者的连续WES报告。WES流程仅专注于先证者，旨在提高诊断能力。我们确定了WES的总体诊断率，并按表型类别、遗传方式、线粒体基因组变异和拷贝数变异（CNV）进行了分析。
在仅对先证者进行诊断性WES检测的2226例患者中，WES的总体诊断率为34.59%（770/2226）。常染色体显性疾病的诊断率最高，为45.58%（351/770），其次是常染色体隐性疾病，为31.95%（246/770），X连锁疾病为9.61%（74/770），线粒体疾病则显著较低，为0.65%（5/770）。12.21%（94/770）的诊断基于从WES数据报告的总共94个拷贝数变异。儿童中的CNV占总CNV的67.02%。虽然大多数分子诊断与核基因相关，但在WES检测中纳入线粒体基因组测序促成了5例诊断。所有线粒体疾病均在成人中被识别。
仅对先证者进行WES检测为一大批患者中的34.59%提供了明确的分子诊断，同时对WES的分析可同步分析单核苷酸变异、外显子、线粒体基因组和CNV，因此与单检测WES方法相比显著提高了诊断率；并有助于识别新的候选基因。
