Li Fang, Yu Miao, Fan Zhuangzhuang, Wu Junyi, Tian Hua, Feng Hailan, Liu Yang, Liu Haochen, Han Dong
Third Clinical Division, Peking University School and Hospital of Stomatology and National Center of Stomatology and National Clinical Research Center for Oral Diseases and National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
Department of Prosthodontics, Peking University School and Hospital of Stomatology and National Center of Stomatology and National Clinical Research Center for Oral Diseases and National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, China.
Front Physiol. 2022 Oct 10;13:1006980. doi: 10.3389/fphys.2022.1006980. eCollection 2022.
Junctional epidermolysis bullosa (JEB) is a group of autosomal recessive disorders characterized by amelogenesis imperfecta (AI) and fragility of the skin and mucous membranes. The purpose of this study was to identify pathogenic gene variants and investigate the phenotypic characteristics of abnormal enamel structure and mucocutaneous lesions in a patient with JEB. Clinical examination of the patient revealed hypoplastic AI, skin lesions, and oral ulcers, whereas her parents were normal. Whole-exome sequencing (WES) and cDNA cloning identified compound heterozygous variants of in the proband: c.125G>C in exon 3, c.1288 + 1G>A in intron 11, and c.1348C>T in exon 12. Among these, c.125G>C was inherited from her father, and the other two variants were inherited from her mother. Functional prediction indicated that the variants might change protein structure and cause disease. Scanning electron microscopy (SEM) examination of the primary and permanent teeth revealed abnormal enamel morphology and microstructures. Hematoxylin-eosin (HE) and immunofluorescence (IF) staining showed significantly abnormal and disorganized epithelial cells in the gingival mucosa. Our results showed that this was a case of intermediate JEB1A (OMIM #226650) with autosomal recessive inheritance. The proband carried rare compound heterozygous variants of . Our results broaden the variant spectrum of the gene and JEB cases. Moreover, this is the first study to identify histological malformations of the primary teeth and oral mucosa in -related patients.
交界型大疱性表皮松解症（JEB）是一组常染色体隐性疾病，其特征为牙釉质发育不全（AI）以及皮肤和黏膜脆弱。本研究旨在鉴定一名JEB患者的致病基因变异，并调查其牙釉质结构异常和黏膜皮肤病变的表型特征。对该患者的临床检查发现其存在牙釉质发育不全、皮肤病变和口腔溃疡，而其父母正常。全外显子组测序（WES）和cDNA克隆鉴定出先证者中的复合杂合变异：外显子3中的c.125G>C、内含子11中的c.1288 + 1G>A以及外显子12中的c.1348C>T。其中，c.125G>C遗传自其父亲，另外两个变异遗传自其母亲。功能预测表明这些变异可能会改变蛋白质结构并导致疾病。对乳牙和恒牙的扫描电子显微镜（SEM）检查显示牙釉质形态和微观结构异常。苏木精-伊红（HE）和免疫荧光（IF）染色显示牙龈黏膜中的上皮细胞明显异常且排列紊乱。我们的结果表明这是一例具有常染色体隐性遗传的中间型JEB1A（OMIM #226650）病例。先证者携带罕见的复合杂合变异。我们的结果拓宽了该基因和JEB病例的变异谱。此外，这是第一项鉴定与相关患者乳牙和口腔黏膜组织学畸形的研究。
