Mutations of COL7A1 gene in three cases of dystrophic epidermolysis bullosa pruriginosa

目的 检测3例痒疹样营养不良型大疱性表皮松解症患者的COL7A1基因突变情况.方法 收集3例患者临床资料,取患者皮损行透射电镜检查.提取3例患者及其相关亲属外周血DNA,应用PCR扩增COL7A1基因的全部外显子及其侧翼序列并测序.结果 病例1及2有家族史,病例3为散发患者.病例1和3皮损透射电镜显示部分区域锚纤维丝轻度减少,病例1可见致密板下裂隙.病例1、2、3的COL7A1基因分别出现c.G6734T、c.G6859A及c.G5318T杂合突变,导致编码氨基酸发生p.G2245V、p.G2287R和p.G1773V突变.突变在病例1和2家族中的患者均呈现共分离现象.病例3父母未带有类似突变.150例无关正常人对照均未发现这三种突变.结论 COL7A1的p.G2245V、p.G2287R和p.G1773V甘氨酸替代突变可能是引起这3例痒疹样营养不良型大疱性表皮松解症患者临床表型的病因,其中p.G2245V、p.G1773V为两种未报道过的新突变.Objective To detect the mutations of COL7A1 gene in three cases of dystrophic epidermolysis bullosa pruriginosa (DEBP). Methods Clinical data were collected from 3 patients with DEBP. Skin lesions were obtained from these patients and subjected to transmission electron microscopy. DNA was extracted from the peripheral blood of the 3 patients, their 16 relatives, and 150 unrelated normal human controls, and PCR was performed to amplify all the exons and flanking sequences of COL7A1 gene followed by sequencing.Results The patient 1 and 2 had family history, whereas the case 3 was sporadic. Transmission electron microscopy showed tissue cleavage beneath lamina densa in case 1 and slightly decreased anchoring fibrils in some areas of the lesions in case 1 and 3. Three heterozygous mutations of COL7A1 gene, i.e., c. G6734T, c.G6859A and c. G5318T, which leaded to three amino acid mutations, i.e., p. G2245V, p. G1773V and p. G2287R, were found in patient 1, 2 and 3 respectively. Of them, p. G2245V and p. G1773V were novel mutations. The mutations strictly cosegregated with the phenotype in the patients of family 1 and 2. No mutation was detected in the unaffected parents of patient 3 or the 150 unrelated healthy controls. Conclusions The p. G2245V, p. G2287Rand p. G1773V mutations of COL7A1 gene may be responsible for the phenotype of DEBP in the three cases,and of them, p. G2245V and p. G1773V have never been reported.中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)03171-1734