痒疹样营养不良型大疱性表皮松解症一家系临床表型及基因突变研究

仵宁1 ，肖生祥2

（1.陕西省咸阳市中心医院皮肤科，陕西 咸阳，712000；2.西安交通大学第二附属医院皮肤科，陕西 西安，710004）

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摘要：

目的 研究1个痒疹样营养不良型大疱性表皮松解症（DEB-Pr）患者家系的基因突变。方法 对1个确诊的DEB-Pr先证者的家系进行现场调查，采集该家系中6 人（4 例患者，2 例健康人）及与该家系无关的健康体检者50例的外周静脉血样本，提取血液中的DNA，采用PCR扩增COL7A1基因的部分外显子，PCR 产物进行序列分析。结果 该家系共有3 代16 人，其中7人患病（男 例，女5例），每代均有患病，符合常染色体显性遗传。皮损表现为胫前，足踝、背部、上肢伸侧痒疹样结节， 伴程度不同的瘙痒、瘢痕、甲受累；家系中检测的4例患者COL7A1 基因第110号外显子存在c.8111G>A，使得COL7A1 基因第2704 位密码子GGA寅GAA，导致编码甘氨酸被谷氨酸替代，系甘氨酸替代突变。同时检测家系中的2 例正常人及与该家系无关的50名健康对照者，未发现该突变。目前该位点突变罕见病例报道。结论 该DEB-Pr家系存在一个新的甘氨酸替代突变，即COL7A1 基因Exon110 c.8111G>A，P.Gly2704Glu（GGA>GAA），这可能是该家系患者发病的分子基础。

关键词：痒疹样营养不良型大疱性表皮松解症；临床表型；基因突变

中图分类号：R758.5文献标志码：A文章编号：2096-1413(2017)26-0001-03

Clinical phenotype and genetic mutation analysis of a pedigree with dystrophic epidermolysis bullosa pruriginosa
WU Ning 1, XIAO Sheng-xiang 2
(1. Department of Dermatology, Xianyang Central Hospital, Xianyang 712000; 2. Department of Dermatology, the Second Affiliated Hospital

of Xi``an Jiaotong University, Xi``an 710004, China)

ABSTRACT: Objective To perform a mutation analysis in a Chinese family with dystrophic epidermolysis bullosa pruriginosa (DEB-Pr). Methods Clinical evaluation was carried out in a pedigree with DEB-Pr through field survey; blood samples were obtained from 6 family individuals (4 affected and 2 unaffected) and 50 unrelated healthy physical examiners, the DNA was extracted from the blood samples; part of COL7A1 exons were amplified using PCR technique for direct sequencing and PCR products were subjected to sequence analysis. Results There were 16 members over 3 generation in this family, of whom, 7 patients (2 males and 5 females) affected DEB-Pr; DEB-Pr was inherited in an autosomal dominant manner in this family. Skin lesions were mainly distributed on the anterior tibial, ankle, back, upper limb extensor pruriginosa nodules, manifested in violaceous papules and nodules and varying degree of pruritus, scars, nails affected; DNA sequencing revealed a novel mutation, c.8111G>A, in the Exon110 of the COL7A1 in 4 affected family members, which leads to a glycine substitution of P.Gly2704Glu (GGA>GAA). The mutation was undetected in either 2 unaffected members or 50 unrelated healthy controls; which is a novel mutation specific to DEB-Pr so far. Conclusion This is a novel glycine substitution, c.8111G >A, P.Gly2704Glu (GGA >GAA) in the Exon110 of the COL7A1 gene, which may be the molecular basis of psthogenesis of DEB-Pr in this family.
KEYWORDS: dystrophic epidermolysis bullosa pruriginosa (DEB-Pr); clinical phenotype; gene mutation

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