Faculty of Medicine, Paediatric Department, Division of Child Neurology, The University of Jordan, Jordan.
Faculty of Medicine, The University of Jordan, Jordan.
Clin Neurol Neurosurg. 2023 Jul;230:107799. doi: 10.1016/j.clineuro.2023.107799. Epub 2023 May 22.
To report the diagnostic yield of clinical singleton whole exome sequencing (WES) performed among a group of Jordanian children presenting with global developmental delay /intellectual disability (GDD/ID), discuss the underlying identified genetic disorders and the challenges encountered.
This retrospective medical record review study included 154 children who were diagnosed with GDD/ID at our clinic at Jordan University Hospital between 2016 and 2021, and whose diagnostic work up included WES.
Consanguinity among parents was reported in 94/154 (61.0%) patients and history of other affected siblings in 35/154 (22.7%) patients. Pathogenic and likely pathogenic variants (solved cases) were reported in 69/154 (44.8%) patients, a variant of uncertain significance was reported in 54/154 (35.0%) and a negative result was reported in 31/154 (20.1%) cases. In the solved cases, autosomal recessive diseases were the most common (33/69; 47.8%). Metabolic disorders were identified in 20/69 (28.9%) patients, followed by developmental and epileptic encephalopathies (9/69; 13.0%) and MECP2 related disorders (7/69; 10.1%). Other single gene disorders were identified in 33/69; 47.8%) patients.
This study had several limitations, as it was hospital-based and only including patients who were able to afford the test. Nevertheless, it yielded several important findings. In resource-limited countries, WES may be a reasonable approach. We discussed the challenges that clinicians meet in the context of shortage of resources.
报告在一组约旦儿童中进行的临床单体全外显子组测序（WES）的诊断率，讨论所确定的遗传疾病，并讨论所遇到的挑战。
本回顾性病历研究包括 2016 年至 2021 年在约旦大学医院我们的诊所诊断为发育迟缓/智力障碍（GDD/ID）的 154 名儿童，他们的诊断工作包括 WES。
94/154（61.0%）名患者的父母有近亲关系，35/154（22.7%）名患者有其他受影响的兄弟姐妹。在 154 名患者中，报告了 69/154（44.8%）患者的致病性和可能致病性变异（已解决病例），54/154（35.0%）患者报告了意义不确定的变异，31/154（20.1%）患者报告了阴性结果。在已解决的病例中，常染色体隐性疾病最常见（33/69；47.8%）。代谢紊乱在 20/69（28.9%）患者中得到识别，其次是发育性和癫痫性脑病（9/69；13.0%）和 MECP2 相关疾病（7/69；10.1%）。在 33/69 名患者中发现了其他单基因疾病（47.8%）。
本研究有几个局限性，因为它是基于医院的，只包括能够负担得起该测试的患者。尽管如此，它仍有几个重要的发现。在资源有限的国家，WES 可能是一种合理的方法。我们讨论了资源短缺情况下临床医生所面临的挑战。
