一例着色性干皮病(XP)伴眼周角化棘皮瘤患者的XP基因突变及角化棘皮瘤组织病理学特征

Mutation of XP Gene and Histopathological Features of Keratoacanthoma in a Patient with Xeroderma Pigmentosum and Periocular Keratoacanthoma

摘要: 目的：探讨着色性干皮病(XP)伴眼周角化棘皮瘤患者的XP基因突变以及角化棘皮瘤组织病理学特征。方法：手术切除该患者眼周角化棘皮瘤并行组织病理学检查。提取该患者外周血白细胞DNA，PCR扩增XP系列基因的编码外显子区域，通过直接测序比较该患者与正常人序列差异以确定致病突变。用MutationTaster在线生物信息学软件分析变异是否有害。结果：术后切除皮损组织送组织病理学检查结果示，表皮角化过度，真皮浅层慢性炎性细胞浸润，肿物与周围界限清楚。经过手术后，电话随访半年恢复良好。基因序列分析结果显示，该患者XP系列基因存在7个错义突变，5个无义突变。错义突变分别位于XPB基因第14外显子的第260位碱基，c. 260A > G (p. Lys 87 Arg)；XPC基因第9外显子的第506位碱基，c. 506T > C (p. Leu169Ser)；第16外显子的第211位碱基，c. 211A > C (p. Ser 71 Arg)；XPF基因第11外显子的第488位碱基，c. 488C > T (p. Pro 163Leu)；XPG基因第2外显子的第50位碱基，c. 50C > T (p. Thr17Met)；第8外显子的第706位碱基，c. 706C > G (p. Leu 236Val)；第15外显子的第346位碱基，c. 346C > G (p. Thr117Met)。无义突变分别位于XPB基因第14外显子的第312位碱基；XPC基因外显子第8外显子的第39位碱基；XPD基因外显子第6外显子的第108位碱基；XPG基因第4外显子的第48位碱基；XPI基因第3外显子的第33位碱基。经MutationTaster在线生物信息学软件分析结果显示：XPC基因第9外显子，c. 506T > C (p. Leu169Ser)，以及XPC基因第16外显子，c. 211A > C (p. Ser 71 Arg)变异为有害突变。结论：该患者确诊为着色性干皮病伴眼周角化棘皮瘤。XPC基因突变(第9外显子，c. 506T > C (p. Leu169Ser)，以及XPC基因第16外显子，c. 211A > C (p. Ser 71 Arg))可能为该患者的致病突变。

Abstract: Objective: To investigate the XP gene mutation and histopathological characteristics of periocular keratoacanthoma in patients with xeroderma pigmentosa (XP). Methods: The periocular keratoacanthoma was resected and histopathological examination was performed. DNA was extracted from peripheral blood leukocytes of the patient, the exon region of XP gene was amplified by PCR. The difference between the patient and the normal was compared by direct sequencing to determine the pathogenic mutation. Results: Histopathological examination showed hyperkeratosis of the epidermis, chronic infiltration of inflammatory cells in the superficial dermis, there is a clear boundary between the tumor and the surrounding. The results of gene sequence analysis showed that there were 7 missense mutations and 5 nonsense mutations in XP gene. The missense mutations were located at c. 260A > G (p. Lys 87 Arg) in exon 14 of XPB gene; c. 506T > C (p. Leu169Ser) in exon 9 and c. 211A > C (p. Ser 71 Arg) in exon 16of XPC gene; c. 488C > T (p. Pro 163Leu) in exon 11 of XPF gene; c. 50C > T (p. Thr17Met) in exon 2, c. 706C > G (p. Leu 236Val) in exon 8 and c. 706C > G (p. Leu 236Val) in exon 15 of XPG gene. The nonsense mutations were located at c. 312A > Gin exon 14 of XPB gene; c. 39T > C in exon 8 of XPC gene, c. 108C > A in exon 6 of XPD gene, c. 48A > T in exon 4 of XPG gene and c. 33C > T in exon 3 of XPI gene. Telephone follow-up for half a year recovered well after the operation. The results showed that c. 506T > C (p. Leu169Ser) in exon 9 and c. 211A > C (p. Ser 71 Arg) in exon 16 of XPC gene, were harmful mutations. Conclusion: The patient was diagnosed as xeroderma pigmentosum with periocular keratoacanthoma. XPC gene mutation (c. 506T > C (p. Leu169Ser) in exon 9 and c. 211A > C (p. Ser 71 Arg) in exon 16) may be pathogenic mutations in this patient.