Importance:Keratinopathic ichthyosis(KPI)represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the KRT1,KRT2,or KRT10 genes.In KPI,the relationship between genotype and phen...Importance:Keratinopathic ichthyosis(KPI)represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the KRT1,KRT2,or KRT10 genes.In KPI,the relationship between genotype and phenotype is complex.Objective:To analyze the clinical manifestations and gene mutations in Chinese patients with KPI.Methods:Clinical data were collected from 13 children diagnosed with KPI,and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel,and the selected variants in the patients and their parents were further validated using the Sanger sequencing method.Results:Genetic analysis identified missense mutations in either KRT1 or KRT10 in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis.A missense hotspot mutation in KRT2 was identified in one patient with superficial epidermolytic ichthyosis.Additionally,two truncation mutations in KRT10 were detected,leading to the development of generalized ichthyosiform erythroderma.Ear malformation and ectropion at birth,scalp involvement,and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti.Interpretation:We analyzed the genotype-phenotype correlations in KPI,revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics.Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.展开更多
目的建立角蛋白I型细胞骨架10[keratin type I cytoskeletal 10,KRT10)和VI型胶原蛋白A3[collagen alpha-3(VI)chain,COL6A3]短肽抗体的ELISA检测方法,并探讨两种瓜氨酸化短肽抗体在类风湿关节炎(rheumatoid arthritis,RA)实验室诊断中...目的建立角蛋白I型细胞骨架10[keratin type I cytoskeletal 10,KRT10)和VI型胶原蛋白A3[collagen alpha-3(VI)chain,COL6A3]短肽抗体的ELISA检测方法,并探讨两种瓜氨酸化短肽抗体在类风湿关节炎(rheumatoid arthritis,RA)实验室诊断中的价值。方法以合成短肽为包被抗原,抗人IgA,IgG及IgM为二抗,检测100例抗瓜氨酸化蛋白抗体(anti-citrullinated protein antibodies,ACPA)阳性组、100例健康对照组和29例RA确诊患者血清中的KRT10,KRT10_C,COL6A3及COL6A3_C短肽抗体水平,比较不同短肽抗体与RA的相关性,采用ROC曲线分析KRT10_C和COL6A3_C短肽抗体对于RA的诊断价值,并对此ELISA方法进行精密度评价。结果与临床诊断相比,KRT10_C短肽抗体诊断RA的灵敏度为58.62%,特异度为52.17%,用于诊断抗CCP抗体阳性RA患者的ROC曲线下面积达0.895;COL6A3_C短肽抗体诊断RA的灵敏度为65.52%,特异度为78.95%,用于诊断抗CCP抗体阴性的RA患者的ROC曲线下面积可达0.956。ELISA检测值KRT10_C(以抗人IgG为二抗)的批内变异系数分别为11.2%(低值)、7.8%(中值)和6.7%(高值)。ELISA检测COL6A3_C(以抗人IgM为二抗)的批内变异系数分别为12.9%(低值)、8.4%(中值)和8.9%(高值)。结论KRT10_C和COL6A3_C短肽抗体对RA诊断具有重要意义,有望加入并完善实验室诊断体系,提高RA的早期诊断率。展开更多
文摘Importance:Keratinopathic ichthyosis(KPI)represents a group of predominantly autosomal dominant genodermatoses resulting from mutations in the KRT1,KRT2,or KRT10 genes.In KPI,the relationship between genotype and phenotype is complex.Objective:To analyze the clinical manifestations and gene mutations in Chinese patients with KPI.Methods:Clinical data were collected from 13 children diagnosed with KPI,and peripheral blood DNA samples were extracted from both the patients and their parents Next-generation sequencing was performed using a congenital ichthyosis multi-gene panel,and the selected variants in the patients and their parents were further validated using the Sanger sequencing method.Results:Genetic analysis identified missense mutations in either KRT1 or KRT10 in ten patients exhibiting varying degrees of severity and distinct features of epidermolytic ichthyosis.A missense hotspot mutation in KRT2 was identified in one patient with superficial epidermolytic ichthyosis.Additionally,two truncation mutations in KRT10 were detected,leading to the development of generalized ichthyosiform erythroderma.Ear malformation and ectropion at birth,scalp involvement,and palmoplantar hyperkeratosis were observed as early signs of ichthyosis with confetti.Interpretation:We analyzed the genotype-phenotype correlations in KPI,revealing that the types and locations of different mutations are associated with distinct phenotypic characteristics.Oral acitretin could be considered a treatment option for severe patients at an appropriate dosage and timing.
文摘目的建立角蛋白I型细胞骨架10[keratin type I cytoskeletal 10,KRT10)和VI型胶原蛋白A3[collagen alpha-3(VI)chain,COL6A3]短肽抗体的ELISA检测方法,并探讨两种瓜氨酸化短肽抗体在类风湿关节炎(rheumatoid arthritis,RA)实验室诊断中的价值。方法以合成短肽为包被抗原,抗人IgA,IgG及IgM为二抗,检测100例抗瓜氨酸化蛋白抗体(anti-citrullinated protein antibodies,ACPA)阳性组、100例健康对照组和29例RA确诊患者血清中的KRT10,KRT10_C,COL6A3及COL6A3_C短肽抗体水平,比较不同短肽抗体与RA的相关性,采用ROC曲线分析KRT10_C和COL6A3_C短肽抗体对于RA的诊断价值,并对此ELISA方法进行精密度评价。结果与临床诊断相比,KRT10_C短肽抗体诊断RA的灵敏度为58.62%,特异度为52.17%,用于诊断抗CCP抗体阳性RA患者的ROC曲线下面积达0.895;COL6A3_C短肽抗体诊断RA的灵敏度为65.52%,特异度为78.95%,用于诊断抗CCP抗体阴性的RA患者的ROC曲线下面积可达0.956。ELISA检测值KRT10_C(以抗人IgG为二抗)的批内变异系数分别为11.2%(低值)、7.8%(中值)和6.7%(高值)。ELISA检测COL6A3_C(以抗人IgM为二抗)的批内变异系数分别为12.9%(低值)、8.4%(中值)和8.9%(高值)。结论KRT10_C和COL6A3_C短肽抗体对RA诊断具有重要意义,有望加入并完善实验室诊断体系,提高RA的早期诊断率。
