Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Dongcheng District, Shuaifuyuan No.1, Beijing, 100730, China.
Department of Endocrinology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100730, China.
Orphanet J Rare Dis. 2021 Jul 3;16(1):296. doi: 10.1186/s13023-021-01933-y.
Autoimmune polyendocrine syndrome type 1 (APS1) is a hereditary disease caused by mutations in the AIRE gene with both endocrine and non-endocrine organ involvement. The existing data from China are limited, and this study aims to describe the phenotypes and genetic characterization in Chinese APS1 patients. In this single-center, retrospective, observational study, comprehensive endocrine and extra-endocrine manifestations were collected, and genetic analysis in AIRE was conducted in patients with APS1 between the years of 1984 and 2018 at Peking Union Medical College Hospital.
In total, 13 patients from 12 unrelated families were enrolled, seven of whom were female, with hypoparathyroidism, chronic mucocutaneous candidiasis, and Addison's disease being the most frequently observed manifestations. Up to 84.7% presented with two or three of the above-mentioned manifestations, and nearly 4.9 ± 1.8 components presented in patients aged 21.2 ± 7.9 years old. Several less common phenotypes, such as myeloproliferative disease, pure red cell aplasia, renal tubular acidosis, asplenia, autoimmune hepatitis, and ankylosing spondylitis, were also observed in patients. Altogether, seven different AIRE mutations were found in six patients, four of which (K161fs, G208V, A246fs, and L308F) had not been previously reported in patients with APS1.
We have provided a comprehensive profile of Chinese patients with APS1, with less commonly observed features being observed in addition to more regularly seen manifestations. Additionally, different AIRE mutations that were observed have expanded the genetic spectrum, which will help with future understanding of the molecular pathogenesis of APS1.
自身免疫性多内分泌腺综合征 1 型（APS1）是一种由 AIRE 基因突变引起的遗传性疾病，涉及内分泌和非内分泌器官。中国现有的数据有限，本研究旨在描述中国 APS1 患者的表型和遗传特征。在这项单中心、回顾性、观察性研究中，我们收集了 APS1 患者的综合内分泌和非内分泌表现，并对 1984 年至 2018 年期间在北京协和医院就诊的 APS1 患者的 AIRE 基因进行了遗传分析。
共纳入 12 个无关家系的 13 例患者，其中 7 例为女性，最常见的表现为甲状旁腺功能减退症、慢性黏膜皮肤念珠菌病和艾迪生病。84.7%的患者表现为上述两种或三种表现，年龄在 21.2±7.9 岁的患者中，近 4.9±1.8 种成分出现。在患者中还观察到一些较不常见的表型，如骨髓增生性疾病、纯红细胞再生障碍、肾小管酸中毒、脾切除、自身免疫性肝炎和强直性脊柱炎。共发现 6 例患者的 7 种不同的 AIRE 突变，其中 4 种（K161fs、G208V、A246fs 和 L308F）在 APS1 患者中尚未报道过。
我们提供了中国 APS1 患者的综合特征，除了更常见的表现外，还观察到较少见的特征。此外，观察到的不同 AIRE 突变扩展了遗传谱，这将有助于未来对 APS1 分子发病机制的理解。
