Netherton Syndrome with a Novel Likely Pathogenic Variant c.420del (p.Ser141ProfsTer5) in SPINK5 Gene: A Case Report

IF 0.9 Q4 DERMATOLOGY
Katya Kovacheva, Zornitza Kamburova, Preslav Vasilev, I. Yordanova
{"title":"Netherton Syndrome with a Novel Likely Pathogenic Variant c.420del (p.Ser141ProfsTer5) in SPINK5 Gene: A Case Report","authors":"Katya Kovacheva, Zornitza Kamburova, Preslav Vasilev, I. Yordanova","doi":"10.1159/000536083","DOIUrl":null,"url":null,"abstract":"Abstract Introduction Netherton syndrome (NS) is a rare autosomal recessive genodermatosis in the group of congenital ichthyosis. The clinical manifestations of the syndrome vary from a very mild clinical manifestation occurring with the picture of ichthyosis linearis circumflexa to exfoliative erythroderma. It can be fatal in the first days of a newborn’s life due to dehydration, hypothermia, weight loss, respiratory infections, and sepsis. A specific anomaly of the hair trichorrexis invaginata is considered pathognomonic for the syndrome. Genetic testing of SPINK5 gene is key to confirming the diagnosis and starting early treatment. Case Presentation We present a case report of NS in a 6-year-old boy who suffered from generalized erythroderma and desquamation of the skin from birth. The patient has atopic diathesis, recurrent skin infections, increased levels of IgE, and delayed physical development. Two genetic variants in SPINK5 gene with clinical significance were identified. The first detected variant is a nonsense mutation, predicted to cause loss of normal protein function either by protein truncation or by nonsense-mediated mRNA decay. The second variant is a likely pathogenic frameshift mutation that truncates the protein in 5 amino acids. The child was treated with acitretin, without satisfactory effect. Conclusion The genetic variant we have described correlates with a severe clinical phenotype of NS. The second genetic variant of the SPINK5 gene, inherited from the father in our case, is novel and has never been published in the literature.","PeriodicalId":9619,"journal":{"name":"Case Reports in Dermatology","volume":null,"pages":null},"PeriodicalIF":0.9000,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Case Reports in Dermatology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1159/000536083","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Abstract Introduction Netherton syndrome (NS) is a rare autosomal recessive genodermatosis in the group of congenital ichthyosis. The clinical manifestations of the syndrome vary from a very mild clinical manifestation occurring with the picture of ichthyosis linearis circumflexa to exfoliative erythroderma. It can be fatal in the first days of a newborn’s life due to dehydration, hypothermia, weight loss, respiratory infections, and sepsis. A specific anomaly of the hair trichorrexis invaginata is considered pathognomonic for the syndrome. Genetic testing of SPINK5 gene is key to confirming the diagnosis and starting early treatment. Case Presentation We present a case report of NS in a 6-year-old boy who suffered from generalized erythroderma and desquamation of the skin from birth. The patient has atopic diathesis, recurrent skin infections, increased levels of IgE, and delayed physical development. Two genetic variants in SPINK5 gene with clinical significance were identified. The first detected variant is a nonsense mutation, predicted to cause loss of normal protein function either by protein truncation or by nonsense-mediated mRNA decay. The second variant is a likely pathogenic frameshift mutation that truncates the protein in 5 amino acids. The child was treated with acitretin, without satisfactory effect. Conclusion The genetic variant we have described correlates with a severe clinical phenotype of NS. The second genetic variant of the SPINK5 gene, inherited from the father in our case, is novel and has never been published in the literature.
患有 SPINK5 基因 c.420del (p.Ser141ProfsTer5) 可能致病的新型变异体的尼瑟顿综合征:病例报告
摘要 引言 尼瑟顿综合征(NS)是先天性鱼鳞病中一种罕见的常染色体隐性遗传皮肤病。该综合征的临床表现各不相同,有的临床表现非常轻微,表现为线状环状鱼鳞病,有的则表现为剥脱性红皮病。由于脱水、体温过低、体重减轻、呼吸道感染和败血症等原因,新生儿在出生后的头几天就可能死亡。一种特殊的毛发异常(trichorrexis invaginata)被认为是该综合征的致病因素。SPINK5 基因的基因检测是确诊和开始早期治疗的关键。病例介绍 我们报告了一例 6 岁男孩的 NS 病例,他从出生起就患有全身性红斑和皮肤脱屑。患者患有特应性病变、反复皮肤感染、IgE水平升高和身体发育迟缓。在 SPINK5 基因中发现了两个具有临床意义的基因变异。第一个变异是无义突变,预计会通过蛋白质截断或无义介导的 mRNA 衰变导致正常蛋白质功能丧失。第二个变异很可能是致病性的换框突变,它使蛋白质被截断了5个氨基酸。患儿接受了阿曲汀治疗,但效果不理想。结论 我们所描述的基因变异与严重的 NS 临床表型相关。在我们的病例中,SPINK5 基因的第二个遗传变异是从父亲那里遗传来的,这是一种新的遗传变异,从未在文献中发表过。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
1.60
自引率
0.00%
发文量
57
审稿时长
9 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信