Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Laboratory Medicine, Seoul National University Hospital, 101, Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
Orphanet J Rare Dis. 2024 Sep 7;19(1):329. doi: 10.1186/s13023-024-03331-6.
Ectodermal dysplasia (ED) is a rare genetic disorder that affects structures derived from the ectodermal germ layer.
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.
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.
外胚层发育不全（ED）是一种罕见的遗传疾病，影响外胚层来源的结构。
本研究分析了 27 例韩国 ED 患者的遗传谱。对 23 例患者进行了全外显子组测序（WES），对其余 4 例患者进行了靶向 panel 测序。在该队列患者中，74.1%（20/27）的患者 ED 检测呈阳性。在这些阳性病例中，80%（16/20）发现 EDA 和 EDAR 突变。值得注意的是，23.1%（3/13）的 EDA 阳性病例存在拷贝数变异。在接受 WES 的 23 例患者中，我们对 8 个知名基因进行了虚拟 panel 分析，诊断出 56.5%（13/23）的病例。此外，对大约 5000 个 OMIM 基因的进一步分析确定了另外 4 个病例，使总阳性率提高了约 17%。这些发现突显了 WES 提高 ED 诊断率的潜力。值得注意的是，94.1%表现出 ED 症状完全三联征（毛发/皮肤/牙齿）的患者存在可检测的 EDA/EDAR 突变。相比之下，没有这三种症状的 7 例患者均未发现 EDA/EDAR 突变。
在进行 ED 的分子诊断时，对于具有典型症状的病例，建议选择 EDA/EDAR 突变的靶向测序，而对于不存在这些症状的病例，WES 被认为是一种有效的策略。
