背景:外胚层发育不良(ED)是一种罕见的遗传性疾病,会影响外胚层胚层的结构。
结果:在这项研究中,我们分析了27例韩国ED患者的基因概况.对23例患者进行全外显子组测序(WES),对其余4例患者进行靶向组测序.在队列中的患者中,74.1%(20/27)的ED检测呈阳性。在这些积极的案例中,在80%(16/20)中发现EDA和EDAR突变。值得注意的是,23.1%(3/13)的EDA阳性病例表现出拷贝数变异。在接受WES的23名患者中,我们对八个知名基因进行了虚拟小组分析,导致56.5%(13/23)的病例诊断。此外,对大约5,000个OMIM基因的进一步分析确定了另外4个病例,将总体阳性率提高约17%。这些发现强调了WES提高ED诊断率的潜力。值得注意的是,94.1%的患者表现出完整的ED症状三联征(头发/皮肤/牙齿)显示可检测的EDA/EDAR突变。相比之下,没有这三种症状的7例患者均未出现EDA/EDAR突变。
结论:进行ED的分子诊断时,对于有经典症状的病例,选择EDA/EDAR突变的靶向测序是可取的,而对于没有这些症状的病例,WES被认为是一种有效的策略。
BACKGROUND: Ectodermal dysplasia (ED) is a rare genetic disorder that affects structures derived from the ectodermal germ layer.
RESULTS: In this study, we analyzed the genetic profiles of 27 Korean patients with ED. Whole exome sequencing (WES) was performed on 23 patients, and targeted panel sequencing was conducted on the remaining 4 patients. Among the patients in the cohort, 74.1% (20/27) tested positive for ED. Of these positive cases, EDA and EDAR mutations were found in 80% (16/20). Notably, 23.1% (3/13) of EDA-positive cases exhibited copy number variations. Among the 23 patients who underwent WES, we conducted a virtual panel analysis of eight well-known genes, resulting in diagnoses for 56.5% (13/23) of the cases. Additionally, further analysis of approximately 5,000 OMIM genes identified four more cases, increasing the overall positivity rate by approximately 17%. These findings underscore the potential of WES for improving the diagnostic yield of ED. Remarkably, 94.1% of the patients manifesting the complete triad of ED symptoms (hair/skin/dental) displayed detectable EDA/EDAR mutations. In contrast, none of the 7 patients without these three symptoms exhibited EDA/EDAR mutations.
CONCLUSIONS: When conducting molecular diagnostics for ED, opting for targeted sequencing of EDA/EDAR mutations is advisable for cases with classical symptoms, while WES is deemed an effective strategy for cases in which these symptoms are absent.