von Schnurbein J, Lahr G, Posovszky C, Debatin K M, Wabitsch M
Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University of Ulm, Ulm, Germany.
J Pediatr Endocrinol Metab. 2008 Oct;21(10):1003-9. doi: 10.1515/jpem.2008.21.10.1003.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive disorder typically presenting with chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal failure variably accompanied by other symptoms. APECED is caused by a mutation in the autoimmune regulator gene (AIRE). Today over 60 different mutations are known world-wide, most of them localized in exons 2, 8, and 10. We report here a German girl with rheumatoid factor positive arthritis, chronic mucocutaneous candidiasis, autoimmune hepatitis, chronic diarrhea, vitiligo, hypothyroidism, hypoparathyroidism, and adrenal failure who is homozygous for a novel mutation at the end of exon 3 of the AIRE gene (c.462G>A), within the conserved splice donor sequence. This mutation probably introduces a frameshift after amino acid 154 (p.Pro154fs) by skipping exon 4. In addition, we analyzed five other family members out of three generations for the AIRE gene mutation and for polymorphisms in the cytotoxic T lymphocyte antigen 4 (CTLA4) gene region and lymphoid protein tyrosine phosphatase (PTPN22) gene, which are associated with the occurrence of sporadic autoimmune Addison's disease, type 1 diabetes mellitus, and generalized vitiligo.
自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）是一种罕见的常染色体隐性疾病，通常表现为慢性黏膜皮肤念珠菌病、甲状旁腺功能减退和肾上腺功能衰竭，并伴有其他各种症状。APECED由自身免疫调节基因（AIRE）突变引起。目前全世界已知有60多种不同的突变，其中大多数位于外显子2、8和10。我们在此报告一名德国女孩，她患有类风湿因子阳性关节炎、慢性黏膜皮肤念珠菌病、自身免疫性肝炎、慢性腹泻、白癜风、甲状腺功能减退、甲状旁腺功能减退和肾上腺功能衰竭，其AIRE基因第3外显子末端（c.462G>A）存在一个新的纯合突变，位于保守的剪接供体序列内。该突变可能通过跳过外显子4在氨基酸154（p.Pro154fs）之后引入移码。此外，我们分析了三代中的其他五名家庭成员的AIRE基因突变以及细胞毒性T淋巴细胞抗原4（CTLA4）基因区域和淋巴样蛋白酪氨酸磷酸酶（PTPN22）基因的多态性，这些基因与散发性自身免疫性 Addison 病、1型糖尿病和全身性白癜风的发生有关。
