1例痒疹样营养不良型大疱性表皮松解症的COL7A1基因突变检测及其临床意义

Mutation detection and clinic significance of COL7A1 in a patient with dystrophic epidermolysis bullosa pruriginosa

目的:研究1例痒疹样营养不良型大疱性表皮松解症(DEB-Pr)家系中的基因突变情况并探讨其临床意义。方法:收集患者的临床资料,取皮损行组织病理学检查及免疫荧光学检查。提取患者及相关亲属外周血DNA,以100例无关正常人外周血DNA作对照,应用PCR扩增COL7A1基因的全部外显子及其侧翼序列并行测序。结果:皮损病理学检查见表皮下水疱,伴数个表皮样囊肿(粟丘疹)形成。患者COL7A1基因出现c.G6235A杂合突变,导致编码Ⅶ型胶原的多肽链发生p.G2079R突变。其父母及弟弟未检出同位点突变,故该病例为散发患者。100例无关正常人对照的COL7A1基因均未发现该位点异常。结论:c.G2079R是引起该家系中患者发生DEB-Pr的特异突变,而非多态性变化,且为de novo突变。该位点突变在国内尚无先例报道,故本研究进一步补充了目前显性遗传DEB-Pr(DDEB-Pr)的突变位点库,并为患者及其家属遗传咨询提供可靠依据。

Objective： To detect gene mutation of COL7A1 in a proband from a family with dystrophic epidermolysis bullosa pruriginosa （DEB-Pr） and discuss its clinic significance. Methods： Clinical data were collected from a patient with DEB-Pr. Histopathological and immunofluorescence examinations were performed. DNA was extracted from peripheral blood of the patient and her relatives, while 100 DNA samples were collected from unrelated normal individuals as controls. PCR was carried out to amplify all the exons and flanking sequences of COL7A1 gene followed by sequencing. Results： Histopathological examination revealed subepidermal bullae with several epidermoid cyst formation（milium）. A c.G6235A transition of COL7A1 was found in the proband, which resulted in p.G2079R substitution in type VII collagen, while the other family members were unaffected. No mutation was found in normal individuals. Conclusions： The mutation of c.G2079R is the underlying cause of DEP-Pr rather than polymorphism in this family, and is referred to as a de novo mutation. The mutation has not been reported domestically before. This study adds to the current DDEB-Pr mutation database and provides reliable basis for patients and their families for genetic counseling.