新生儿遗传性营养不良性大疱性表皮松解症基因诊断1例  

Neonatal hereditary dystrophic epidermolysis bullosa: a genetically diagnosed case report

作　　者：姜毅[1] 侯新琳[1] 李昕[1] 林志淼[2] 崔晨[1] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]北京大学第一医院皮肤科,北京100034

出　　处：《北京大学学报（医学版）》2013年第2期202-206,共5页Journal of Peking University:Health Sciences

摘　　要：目的:探讨临床表现、皮肤活检病理诊断和基因诊断在遗传性营养不良性大疱性表皮松解症的诊断意义。方法:分析1例新生儿起病的遗传性营养不良性大疱性表皮松解症的临床和病理特点和基因诊断结果。结果:1例生后10 h入院新生儿,出生后即发现下肢有大片皮肤破损和糜烂,病变延伸至左侧踝关节和足底,住院后发现口腔内有血疱和水疱,住院期间皮肤受压和摩擦处多处出现新的大疱和皮肤脱落及皮肤糜烂。皮肤糜烂处分泌物和口腔分泌物细菌涂片和培养均未见细菌。取患儿皮肤做病理检查,结果光镜下可见真皮内有少量疏松结缔组织。电子显微镜下真皮层仅见少量纤维母细胞和胶原纤维,基质结构不清。大部分区域未见基底层,张力丝零散分布在真皮组织,部分区域有基底膜,但锚纤维结构不清,致密层变薄,符合遗传性营养不良性大疱性表皮松解症诊断标准。取患儿及其父母静脉血进行COL7A1基因检测,其母在COL7A1基因第13个外显子500上插入AGGG片段,其父在第98个外显子序列后剪切位点有一个G突变为A。患儿COL7A1基因出现复合杂合突变;突变位点分别与父亲和母亲位点一致,证实患儿遗传了来自父、母亲双方的突变基因,因此发病,其父母为表型正常的致病基因携带者。结论:对于临床怀疑遗传性大疱性表皮松解症患儿应先做皮肤病理检查,特别是通过电子显微镜超微结构观察做出初步分型,再根据病理类型进一步做相应基因检测确诊,如能对父母同时进行基因检测对今后优生可能有很大帮助。Objective：To investigate the diagnostic value of clinical manifestations, pathologic findings of skin biopsies and genetic testing in the diagnosis of neonatal hereditary dystrophic epidermolysis bullo-sa. Methods： Here we reported one case of hereditary dystrophic epidermolysis bullosa with neonatal on-set, and explored the clinical and pathological features, as well as the genetic diagnosis, of the disease process. Results： The neonate was born with large areas of skin damage and erosion, extending to the left ankle and foot, and was admitted to the hospital 10 hours after birth. Hemophysallis and blisters were found in her mouth, and during her hospital stay the patient developed multiple bullae, skin peeling and skin erosion at the compressed and friction areas of the body. Bacterial cultures from both the skin erosion and oral secretions were negative. Pathology of the skin showed a small amount of loose connective tissue visualized by light microscopy. Visualization with electron microscope revealed no basal layer in the ma- jority of the skin, tonofilament scattered in the dermal tissue, and basement membrane with unclear an-choring fibril and thinner lamina densa in a portion of the region studied. Consequently, the diagnosis of dystrophic epidermolysis bullosa was made. COLTA1 gene tests were subsequently performed on the pa-tient＇s family. Insertion of AGGG fragment was found at the 500th locus of exon 13 in the mother＇s COL7A1 gene. The patient＇ s father had a G-to-A mutation at the splicing locus after exon 98. The neo- nate had complex heterozygous mutation in COL7A1 gene consistent with the father and mother＇ s muta- tion, which led to the development of the disease. The parents, who were carriers of the disease-causing genes, both had a normal phenotype. Conclusion： Skin pathology was indicated for the diagnosis of clini-cally suspicious hereditary dystrophic epidermolysis bullosa. The microstrncture visualized in the patho-logic findings aided in making the preliminary classificati

关 键 词：表皮松解 大疱性 营养不良性 基因检测 婴儿 新生 

分 类 号：R758.59[医药卫生—皮肤病学与性病学]