先天性甲肥厚合并疑似Ogna型单纯型大疱性表皮松解症一家系调查

Pachyonychia congenita complicated by epidermolysis bullosa simplex Ogna:a pedigree analysis

患者男,23岁,双足底反复糜烂、疼痛10年,行走困难半月。皮肤科检查:患者全部指(趾)甲肥厚,呈黑褐色,甲远端隆起,甲下有硬性角质样物质填充。双足底角化明显,浸渍呈乳白色,双足跖及侧缘见弥漫性丘疱疹,散在糜烂面,手腕及额部见水疱。前臂、肘部伸侧散在毛囊性丘疹及细碎脱屑,舌表面弥漫性白斑。符合先天性甲肥厚临床表现。抽取患者及其父母、祖母外周血行全基因组外显子测序,结果显示,患者及其父亲存在先天性厚甲综合症K6a型KRT6A基因1号外显子第516~518位碱基缺失(c.516-518delCAA),同时存在PLEC基因27号外显子第3970位碱基替换(c.3970C>T)。该突变型可能致Ogna型单纯型大疱性表皮松解症。患者祖母存在与患者相同的PLEC基因突变。诊断:先天性甲肥厚且疑似Ogna型单纯型大疱性表皮松解症。予阿维A治疗9个月,患者指甲颜色、足底症状明显缓解,腕部散在粟粒样水疱消失。目前随访中。

A 23-year-old male patient presented with repeated painful erosion on the soles of both feet for 10 years,and with walking difficulties for half a month.Skin examination showed thick dark-brown finger and toe nails with distal protuberance,and hard keratinous materials under the nails.Obvious hyperkeratosis and maceration occurred on the soles of both feet,which appeared milky-white in color;diffuse papulovesicles were observed on the soles and lateral margins of both feet with scattered erosions.Vesicles were observed on the wrist and forehead.Follicular papules and fine scales were scattered on the extensor aspect of the forearm and elbow,and diffuse white patches were observed on the surface of the tongue.The above clinical manifestations were consistent with pachyonychia congenita.Peripheral blood samples were obtained from the patient,his parents and grandmother,and subjected to whole-exome sequencing.Sequencing showed two mutations in both the patient and his father,including base deletions at position 516-518(c.516-518 del CAA)in exon 1 of the KRT6A gene,which caused pachyonychia congenita-K6a,and a base substitution at position 3 970(c.3970 C>T)in exon 27 of the PLEC gene,which may cause epidermolysis bullosa simplex Ogna.The same mutation in the PLEC gene was found in the patient′s grandmother.The patient was diagnosed with pachyonychia congenita complicated by suspected epidermolysis bullosa simplex Ogna.After 9-month treatment with acitretin,the nails became lighter in color,plantar skin lesions were obviously relieved,and scattered millet-like vesicles in the wrist completely subsided.The patient was followed up at present.