Importance:Nagashima-type palmoplantar keratosis(NPPK)is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7.Despite the increasing interest in readthrough gentamicin treatment of NPPK,clinical ev...Importance:Nagashima-type palmoplantar keratosis(NPPK)is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7.Despite the increasing interest in readthrough gentamicin treatment of NPPK,clinical evidence for this treatment is limited.Objective:This study aimed to provide further evidence for the use of topical gentamicin in the treatment of NPPK in children with nonsense mutations.Methods:We designed a bilaterally controlled study of topical gentamicin ointment.Children diagnosed with NPPK carrying nonsense mutations were enrolled in this study.A 0.1%gentamicin ointment was applied to one hand and an emollient to the other for 3 months.A bilateral comparison of the visual analog scale scores for clinical manifestations and safety was performed.Results:Ten children with NPPK were included in this study.In comparison with the emollient side,the topical gentamicin side showed significant improvements in hyperkeratosis,erythema,maceration,and desquamation after 1 and 3 months of treatment(P<0.05).However,hyperhidrosis and odor did not improve significantly.No adverse events were observed during the systemic safety monitoring examinations.Interpretation:Topical gentamicin ointment showed good safety in the treatment of NPPK with nonsense mutations,indicating that it is a promising therapeutic choice in children with NPPK.展开更多
目的：报告2例长岛型掌跖角化病，确定其致病基因突变。方法收集患者及其父母外周血和临床资料，提取基因组 DNA，PCR 扩增 SERPINB7基因8个外显子及其侧翼序列，对扩增产物进行 DNA 测序以查找基因突变位点，并以200例无关健康人 DNA ...目的：报告2例长岛型掌跖角化病，确定其致病基因突变。方法收集患者及其父母外周血和临床资料，提取基因组 DNA，PCR 扩增 SERPINB7基因8个外显子及其侧翼序列，对扩增产物进行 DNA 测序以查找基因突变位点，并以200例无关健康人 DNA 作为对照进行扩增测序。结果2例患者均存在 SERPINB7基因 c.796C 〉 T 纯合突变，导致编码蛋白质第266位氨基酸出现终止改变（p.R266＊），其父母均为 c.796C 〉 T 杂合突变，而无关健康对照未发现上述突变。结论 SERPINB7基因的 c.796C 〉 T 突变可能是引起2例患者长岛型掌跖角化病的原因。展开更多
Background The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic.However,in the past decade,there were considerable interests in therapeutic approaches in...Background The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic.However,in the past decade,there were considerable interests in therapeutic approaches in treating hereditary diseases.Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins.Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins.We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases.Data sources We search the MEDLINE through PubMed,EMBASE databases,and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms"gentamicin,topical gentamicin,genodermatosis,genetic skin diseases".Results The application of gentamicin in genodermatosis yielded promising results,both in vivo and in vitro,including Nagashima-type palmoplantar keratosis,epidermolysis bullosa,Hailey-Hailey disease,hereditary hypotrichosis simplex of the scalp,etc.Conclusions Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.展开更多
基金Children’s Medicine Research Project of Beijing Children’s Hospital,Capital Medical University,Grant/Award Number:YZZD202002
文摘Importance:Nagashima-type palmoplantar keratosis(NPPK)is a hereditary dermatosis mostly caused by a nonsense mutation in SERPINB7.Despite the increasing interest in readthrough gentamicin treatment of NPPK,clinical evidence for this treatment is limited.Objective:This study aimed to provide further evidence for the use of topical gentamicin in the treatment of NPPK in children with nonsense mutations.Methods:We designed a bilaterally controlled study of topical gentamicin ointment.Children diagnosed with NPPK carrying nonsense mutations were enrolled in this study.A 0.1%gentamicin ointment was applied to one hand and an emollient to the other for 3 months.A bilateral comparison of the visual analog scale scores for clinical manifestations and safety was performed.Results:Ten children with NPPK were included in this study.In comparison with the emollient side,the topical gentamicin side showed significant improvements in hyperkeratosis,erythema,maceration,and desquamation after 1 and 3 months of treatment(P<0.05).However,hyperhidrosis and odor did not improve significantly.No adverse events were observed during the systemic safety monitoring examinations.Interpretation:Topical gentamicin ointment showed good safety in the treatment of NPPK with nonsense mutations,indicating that it is a promising therapeutic choice in children with NPPK.
文摘目的：报告2例长岛型掌跖角化病，确定其致病基因突变。方法收集患者及其父母外周血和临床资料，提取基因组 DNA，PCR 扩增 SERPINB7基因8个外显子及其侧翼序列，对扩增产物进行 DNA 测序以查找基因突变位点，并以200例无关健康人 DNA 作为对照进行扩增测序。结果2例患者均存在 SERPINB7基因 c.796C 〉 T 纯合突变，导致编码蛋白质第266位氨基酸出现终止改变（p.R266＊），其父母均为 c.796C 〉 T 杂合突变，而无关健康对照未发现上述突变。结论 SERPINB7基因的 c.796C 〉 T 突变可能是引起2例患者长岛型掌跖角化病的原因。
基金supported by Children's Medicine Research Project of Beijing Children's Hospital,Capital Medical University(YZZD202002).
文摘Background The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic.However,in the past decade,there were considerable interests in therapeutic approaches in treating hereditary diseases.Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins.Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins.We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases.Data sources We search the MEDLINE through PubMed,EMBASE databases,and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms"gentamicin,topical gentamicin,genodermatosis,genetic skin diseases".Results The application of gentamicin in genodermatosis yielded promising results,both in vivo and in vitro,including Nagashima-type palmoplantar keratosis,epidermolysis bullosa,Hailey-Hailey disease,hereditary hypotrichosis simplex of the scalp,etc.Conclusions Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.
