Dowling-Degos病1家系KRT5基因新突变分析

doi:10.35541/cjd.20210028

中华皮肤科杂志 ›› 2022, Vol. 55 ›› Issue (8): 703-705.doi: 10.35541/cjd.20210028

Dowling-Degos病1家系KRT5基因新突变分析

魏瑾¹ 臧东杰² 曾三武² 蒋靖³ 伦文辉¹

¹首都医科大学附属北京地坛医院皮肤性病科，北京 100015；²天津市第一中心医院皮肤科，天津 300192；³天津市南开医院皮肤科，天津 300100

收稿日期:2021-01-11 修回日期:2021-08-17 发布日期:2022-08-02
通讯作者: 臧东杰；伦文辉 E-mail:zangdongjie@126.com; lunwenhui@163.com
基金资助:
皮肤病学教育部重点实验室开放课题基金（AY2017-1-004）

Mutation analysis of the KRT5 gene in a Chinese pedigree with Dowling-Degos disease

Wei Jin¹, Zang Dongjie², Zeng Sanwu², Jiang Jing³, Lun Wenhui¹

¹Department of Dermatology and Venereology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China; ²Department of Dermatology, Tianjin First Central Hospital, Tianjin 300192, China; ³Department of Dermatology, Tianjin Nankai Hospital, Tianjin 300100, China

Received:2021-01-11 Revised:2021-08-17 Published:2022-08-02
Contact: Zang Dongjie; Lun Wenhui E-mail:zangdongjie@126.com; lunwenhui@163.com
Supported by:
Open Project Fund of the Key Lab of Dermatology, Ministry of Education（AY2017-1-004）

摘要/Abstract

摘要： 【摘要】目的分析Dowling-Degos病1家系KRT5基因突变情况。方法收集先证者临床资料，调查先证者家族3代共12人信息，采集先证者和8例家系成员以及家系以外50例无亲缘关系的健康人外周血，提取基因组DNA行全外显子测序后与人类基因组KRT5、POFUT1及POGLUT1序列进行比对。结果本家系有3例患者，分别为先证者及其父亲和祖母（去世）。先证者及其父亲临床表现为皱褶部网状色素沉着，以胸腹皱褶部位为重，且KRT5基因第一外显子均存在c.165T>A杂合无义突变，其他家系成员及健康对照均未发现此突变，所有受试者POFUT1及POGLUT1基因检测未见异常。结论本研究新发现1处KRT5基因c.165T>A突变，导致先证者及其父Dowling-Degos病。

关键词: 皮肤色素沉着, 皮肤疾病, 遗传性, Dowling-Degos病, KRT5基因

Abstract: 【Abstract】 Objective To investigate mutations in the KRT5 gene in a pedigree with Dowling-Degos disease. Methods Clinical data were collected from the proband, and a survey was conducted in 12 members in 3 generations of the family. Peripheral blood samples were obtained from the proband, 8 family members and 50 unrelated healthy individuals, genomic DNA was extracted for whole-exome sequencing, and sequencing results were compared with the sequences of human KRT5, POFUT1 and POGLUT1 genes. Results There were 3 patients in this family, including the proband, his father and deceased grandmother. The proband and his father clinically presented with reticular pigmentation in the skinfolds, especially the chest and abdomen skinfolds. A novel heterozygous nonsense mutation c.165T>A was identified in exon 1 of the KRT5 gene in the proband and his father, but not in other family members or healthy controls. No abnormality was found in the POFUT1 or POGLUT1 gene in any subjects. Conclusion A novel heterozygous nonsense mutation c.165T>A was identified in the KRT5 gene, and may contribute to the clinical phenotype of the proband and his father with Dowling-Degos disease.

Key words: Skin pigmentation, Skin diseases, genetic, Dowling-Degos disease, KRT5 gene

魏瑾臧东杰曾三武蒋靖伦文辉. Dowling-Degos病1家系KRT5基因新突变分析[J]. 中华皮肤科杂志, 2022,55(8):703-705. doi:10.35541/cjd.20210028

Wei Jin, Zang Dongjie, Zeng Sanwu, Jiang Jing, Lun Wenhui. Mutation analysis of the KRT5 gene in a Chinese pedigree with Dowling-Degos disease[J]. Chinese Journal of Dermatology, 2022, 55(8): 703-705.doi:10.35541/cjd.20210028

参考文献 16

［1］	Stephan C, Kurban M, Abbas O. Dowling⁃Degos disease: a review［J］. Int J Dermatol, 2021,60（8）:944⁃950. doi: 10.1111/ijd.15385.
［2］	刘薇, 刘佳玮, 马东来. Dowling⁃Degos病［J］. 临床皮肤科杂志, 2017,46（10）:700⁃702. doi: 10.16761/j.cnki.1000⁃4963.2017. 10.008.
［3］	Kiuru M, Terrell JR, Gorouhi F, et al. Novel POFUT1 mutation in patient with flexural and acral hyperpigmented reticulated macules presenting in adolescence［J］. JAAD Case Rep, 2020,6（4）:334⁃336. doi: 10.1016/j.jdcr.2020.02.016.
［4］	Betz RC, Planko L, Eigelshoven S, et al. Loss⁃of⁃function mutations in the keratin 5 gene lead to Dowling⁃Degos disease［J］. Am J Hum Genet, 2006,78（3）:510⁃519. doi: 10.1086/500850.
［5］	González⁃Villanueva I, Gutiérrez M, Hispán P, et al. Novel POFUT1 mutation associated with hidradenitis suppurativa⁃Dowling⁃Degos disease firm up a role for Notch signalling in the pathogenesis of this disorder［J］. Br J Dermatol, 2018,178（4）:984⁃986. doi: 10.1111/bjd.16264.
［6］	Basmanav FB, Oprisoreanu AM, Pasternack SM, et al. Mutations in POGLUT1, encoding protein O⁃glucosyltransferase 1, cause autosomal⁃dominant Dowling⁃Degos disease［J］. Am J Hum Genet, 2014,94（1）:135⁃143. doi: 10.1016/j.ajhg.2013.12.003.
［7］	Jones EW, Grice K. Reticulate pigmented anomaly of the flexures. Dowing Degos disease, a new genodermatosis［J］. Arch Dermatol, 1978,114（8）:1150⁃1157.
［8］	Pavlovsky M, Sarig O, Eskin⁃Schwartz M, et al. A phenotype combining hidradenitis suppurativa with Dowling⁃Degos disease caused by a founder mutation in PSENEN［J］. Br J Dermatol, 2018,178（2）:502⁃508. doi: 10.1111/bjd.16000.
［9］	吉津, 李明, 赖美玲, 等. 屈侧网状色素沉着一家系调查及KRT5基因突变检测［J］. 中华皮肤科杂志, 2012,45（4）:272⁃274. doi: 10.3760/cma.j.issn.0412⁃4030.2012.04.016.
［10］	鲁楠, 李晶辉, 刘红, 等. 屈侧网状色素异常一家系角蛋白5基因突变研究［J］. 中国麻风皮肤病杂志, 2012,28（2）:79⁃81. doi: 10.3969/j.issn.1009⁃1157.2012.02.002.
［11］	陈源昊琪, 董辉, 杨彪, 等. 屈侧网状色素沉着症一家系POFUT1基因突变分析［J］. 宁夏医科大学学报, 2018,40（1）:47⁃50. doi: 10.16050/j.cnki.issn1674⁃6309.2018.01.011.
［12］	Kossard S, Krivanek J. Dowling⁃Degos disease⁃⁃a heat aggravated variant［J］. Australas J Dermatol, 2001,42（3）:214⁃216. doi: 10.1046/j.1440⁃0960.2001.00521.x.
［13］	Li M, Cheng R, Liang J, et al. Mutations in POFUT1, encoding protein O⁃fucosyltransferase 1, cause generalized Dowling⁃Degos disease［J］. Am J Hum Genet, 2013,92（6）:895⁃903. doi: 10. 1016/j.ajhg.2013.04.022.
［14］	Garcovich S, Tricarico PM, Nait⁃Meddour C, et al. Novel nicastrin mutation in hidradenitis suppurativa⁃Dowling⁃Degos disease clinical phenotype: more than just clinical overlap?［J］. Br J Dermatol, 2020,183（4）:758⁃759. doi: 10.1111/bjd.19121.
［15］	Ralser DJ, Basmanav FB, Tafazzoli A, et al. Mutations in γ⁃secretase subunit⁃encoding PSENEN underlie Dowling⁃Degos disease associated with acne inversa［J］. J Clin Invest, 2017,127（4）:1485⁃1490. doi: 10.1172/JCI90667.
［16］	Zhang J, Li M, Yao Z. Updated review of genetic reticulate pigmentary disorders［J］. Br J Dermatol, 2017,177（4）:945⁃959. doi: 10.1111/bjd.15575.

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Dowling-Degos病1家系KRT5基因新突变分析

Mutation analysis of the KRT5 gene in a Chinese pedigree with Dowling-Degos disease

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