非典型可变性红斑角化症1例的临床与遗传学分析
收稿日期: 2025-02-17
录用日期: 2025-04-17
网络出版日期: 2025-06-01
基金资助
国家自然科学基金项目(81903197);上海交通大学医学院附属新华医院基金项目(18YJ22)
Clinical and genetic analysis of atypical erythrokeratodermia variabilis: a case report
Received date: 2025-02-17
Accepted date: 2025-04-17
Online published: 2025-06-01
目的 总结1例因GJB3基因变异导致的非典型可变性红斑角化症（EKV）患儿的临床表现和基因检测结果，为临床医师提供参考。方法 收集1例就诊于本院皮肤科的EKV患儿的临床资料，采集患儿及其父母外周血DNA，应用二代靶向富集测序鉴定致病变异，并用Sanger测序验证。结果 患儿，男，16岁，因“全身干燥，面部红斑和躯干四肢角化过度性斑块16年”就诊于本院皮肤科。查体发现患儿面部瘙痒性红斑和全身角化过度，通过二代靶向富集测序和Sanger测序发现患儿GJB3基因的杂合错义突变c.256T>A(p.C86S)，患儿父母未检出该变异。根据临床表现及基因检测结果，患儿最终被诊断为EKV。结论 本研究报道了1例与GJB3基因致病变异相关的皮损表现特殊的EKV，有助于提高皮肤科医师对该病的临床认知。
马毓芝 , 姚志荣 , 张佳 . 非典型可变性红斑角化症1例的临床与遗传学分析[J]. 临床儿科杂志, 2025 , 43(6) : 470 -474 . DOI: 10.12372/jcp.2025.25e0116
Objective To summarize the clinical manifestations and gene detection results of a child with atypical erythrokeratodermia variabilis (EKV) caused by GJB3 gene variation, and provide reference for clinicians. Methods The clinical data of a child with EKV who was admitted to the Dermatology Department of our hospital were collected. The peripheral blood DNA of the child and his parents was collected, and the pathogenic variation was identified by second-generation targeted enrichment sequencing, and verified by Sanger sequencing. Results The patient, a 16-year-old boy, visited the hospital due to "generalized dryness, facial erythema and hyperkeratotic plaques on the trunk and limbs for 16 years". Physical examination revealed pruritic erythema on the face and generalized hyperkeratosis. Through next-generation targeted enrichment sequencing and Sanger sequencing, a heterozygous missense mutation of c.256T>A (p.C86S) in the GJB3 gene was identified in the patient. The mutation was not detected in the patient's parents. Based on the clinical manifestations and genetic testing results, the patient was ultimately diagnosed with EKV. Conclusions This study reports a case of EKV with special skin lesions caused by pathogenic variants in the GJB3 gene, which is helpful for improving the clinical cognition of dermatologists on this disease.
| [1] | Ishida-Yamamoto A. Erythrokeratodermia variabilis et progressiva[J]. J Dermatol, 2016, 43(3): 280-285. |
| [2] | Common JE, O'Toole EA, Leigh IM, et al. Clinical and genetic heterogeneity of erythrokeratoderma variabilis[J]. J Invest Dermatol, 2005, 125(5): 920-927. |
| [3] | Balci DD, Yaldiz M. Erythrokeratodermia variabilis: successful palliative treatment with acitretin[J]. Indian J Dermatol Venereol Leprol, 2008, 74(6): 649-650. |
| [4] | Richard G, Smith LE, Bailey RA, et al. Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis[J]. Nat Genet, 1998, 20(4): 366-369. |
| [5] | Yang Z, Qi Z, Xu Z, et al. Congenital ichthyosiform erythroderma with a novel variant in ABCA12 in a Chinese patient[J]. Pediatr Investig, 2020, 4(1): 51-54. |
| [6] | Eskin-Schwartz M, Drozhdina M, Sarig O, et al. Epidermolytic ichthyosis sine epidermolysis[J]. Am J Dermatopathol, 2017, 39(6): 440-444. |
| [7] | Bakhchane A, Kindil Z, Charoute H, et al. Compound heterozygous SLC29A3 mutation causes H syndrome in a Moroccan patient: A case report[J]. Curr Res Transl Med, 2016, 64(2): 65-68. |
| [8] | Oh DY, Jung KE, Lee JS, et al. A case of erythro-keratodermia variabilis in Korean[J]. Ann Dermatol, 2019, 31(Suppl): S49-S51. |
| [9] | Richard G, Brown N, Smith LE, et al. The spectrum of mutations in erythrokeratodermias--novel and de novo mutations in GJB3[J]. Hum Genet, 2000, 106(3): 321-329. |
| [10] | Wilgoss A, Leigh IM, Barnes MR, et al. Identification of a novel mutation R42P in the gap junction protein beta-3 associated with autosomal dominant erythrokeratoderma variabilis[J]. J Invest Dermatol, 1999, 113(6): 1119-1122. |
| [11] | Shah M, Baral S, Adhikari RC. Erythrokeratoderma variabilis (EKV) - first Nepalese case documenting GJB3 mutation[J]. Skin Health Dis, 2021, 1(4): e63. |
| [12] | Glatz M, van Steensel MA, van Geel M, et al. An unusual missense mutation in the GJB3 gene resulting in severe erythrokeratodermia variabilis[J]. Acta Derm Venereol, 2011, 91(6): 714-715. |
| [13] | Imura K, Ikeya S, Ogata T, et al. Erythrokeratodermia variabilis et progressiva with a rare GJB3 mutation[J]. J Dermatol, 2020, 47(4): e111-e113. |
| [14] | Morley SM, White MI, Rogers M, et al. A new, recurrent mutation of GJB3 (Cx31) in erythrokeratodermia variabilis[J]. Br J Dermatol, 2005, 152(6): 1143-1148. |
| [15] | Otaguchi R, Kawakami T, Matsuoka M, et al. A sporadic elder case of erythrokeratodermia variabilis with a single base-pair transversion in GJB3 gene successfully treated with systemic vitamin A derivative[J]. J Dermatol, 2014, 41(11): 1016-1018. |
| [16] | Feldmeyer L, Plantard L, Mevorah B, et al. Novel mutation of connexin 31 causing erythrokeratoderma variabilis[J]. Br J Dermatol, 2005, 152(5): 1072-1074. |
| [17] | Wang ZX, Lu WS, Li H, et al. A novel GJB3 (Cx31) missense mutation in a Chinese patient with erythrokeratodermia variabilis[J]. J Eur Acad Dermatol Venereol, 2011, 25(1): 113-115. |
| [18] | Renner R, Paasch U, Simon JC, et al. A new mutation in the GJB3 gene in a patient with erythrokeratodermia variabilis[J]. J Eur Acad Dermatol Venereol, 2008, 22(6): 750-751. |
| [19] | Deng Y, Wang H, Mou Y, et al. Exome sequencing identifies novel compound heterozygous mutations in GJB3 gene that cause erythrokeratodermia variabilis et progressiva[J]. Australas J Dermatol, 2019, 60(1): e87-e89. |
| [20] | Fuchs-Telem D, Pessach Y, Mevorah B, et al. Erythrokeratoderma variabilis caused by a recessive mutation in GJB3[J]. Clin Exp Dermatol, 2011, 36(4): 406-411. |
| [21] | Gottfried I, Landau M, Glaser F, et al. A mutation in GJB3 is associated with recessive erythrokeratodermia variabilis (EKV) and leads to defective trafficking of the connexin 31 protein[J]. Hum Mol Genet, 2002, 11(11): 1311-1316. |
| [22] | Wang W, Liu LH, Chen G, et al. A missense mutation in the GJB3 gene responsible for erythrokeratodermia variabilis in a Chinese family[J]. Clin Exp Dermatol, 2012, 37(8): 919-921. |
| [23] | Gao Y, Zhang Q, Zhang S, Yang L, Liu Y, Liu Y, Wang T. A connexin gene (GJB3) mutation in a Chinese family with erythrokeratodermia variabilis, ichthyosis and nonsyndromic hearing loss: case report and mutations update[J]. Front Genet, 2022, 13: 797124. |
| [24] | Terrinoni A, Leta A, Pedicelli C, et al. A novel recessive connexin 31 (GJB3) mutation in a case of erythrokeratodermia variabilis[J]. J Invest Dermatol, 2004, 122(3): 837-839. |
| [25] | Scott CA, Kelsell DP. Key functions for gap junctions in skin and hearing[J]. Biochem J, 2011, 438(2):245-254. |
| [26] | Sugiura K, Arima M, Matsunaga K, et al. The novel GJB3 mutation p.Thr202Asn in the M4 transmembrane domain underlies erythrokeratodermia variabilis[J]. Br J Dermatol, 2015, 173(1): 309-311. |
| [27] | 王雯. 可变性红斑角化症一家系GJB3和GJB4基因突变研究[D]. 安徽: 安徽医科大学, 2012. |
| [28] | 周欣, 任军, 田歆, 等. 二例可变性红斑角化症患者GJB3、4基因突变研究[J]. 中华皮肤科杂志, 2012, 45(2): 129-130. |
| Zhou X, Ren J, Tian X, et al. Study on GJB3 and GJB4 gene mutations in two patients with variable red spot keratosis[J]. Zhonghua Pifuke Zazhi, 2012, 45(2): 129-130. | |
| [29] | 刘红, 付希安, 张福仁. 4例可变性红斑角化症的基因突变检测[J]. 中国麻风皮肤病杂志, 2011, 27(5): 304-306. |
| Liu H, Fu XA, Zhang FR. Detection of gene mutations in four cases of variable erythrodermic ichthyosis[J]. Zhongguo Mafeng Pifubing Zazhi, 2011, 27(5): 304-306. | |
| [30] | 张莹, 陈浩, 孙建方. GJB3基因纯合突变致可变性红斑角化症一例[J]. 中华皮肤科杂志, 2020, 53(11) : 936-937. |
| Zhang Y, Chen H, Sun JF. A case of variable erythrokeratoderma caused by homozygous mutation of GJB3 gene[J]. Zhonghua Pifuke Zazhi, 2020, 53(11): 936-937. |
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