Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva

Abstract Background Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJ...

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Main Authors: Changxing Li, Jingyao Liang, Pingjiao Chen, Kang Zeng, Rujun Xue, Xin Tian, Liuping Liang, Qi Wang, Minglan Shi, Xibao Zhang
Format: Article
Language:English
Published: Wiley 2019-06-01
Series:Molecular Genetics & Genomic Medicine
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Online Access:https://doi.org/10.1002/mgg3.670
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spelling doaj-d6e8c59abdec4436a8a9d20f6695fb892020-11-24T20:55:57ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-06-0176n/an/a10.1002/mgg3.670Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressivaChangxing Li0Jingyao Liang1Pingjiao Chen2Kang Zeng3Rujun Xue4Xin Tian5Liuping Liang6Qi Wang7Minglan Shi8Xibao Zhang9Department of Dermatology Nanfang Hospital, Southern Medical University Guangzhou ChinaDepartment of Dermatology Guangzhou Institute of Dermatology Guangzhou ChinaDepartment of Dermatology Nanfang Hospital, Southern Medical University Guangzhou ChinaDepartment of Dermatology Nanfang Hospital, Southern Medical University Guangzhou ChinaDepartment of Dermatology Guangzhou Institute of Dermatology Guangzhou ChinaDepartment of Dermatology Guangzhou Institute of Dermatology Guangzhou ChinaDepartment of Dermatology Nanfang Hospital, Southern Medical University Guangzhou ChinaDepartment of Dermatology Nanfang Hospital, Southern Medical University Guangzhou ChinaDepartment of Dermatology Nanfang Hospital, Southern Medical University Guangzhou ChinaDepartment of Dermatology Guangzhou Institute of Dermatology Guangzhou ChinaAbstract Background Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJB4 have been reported to cause EKVP. Here, we report the identification of two de novo missense mutations in the GJA1 gene in two unrelated individuals with EKVP. Methods The patients and his family members were subjected to mutation detection in the candidate gene GJA1, GJB3, and GJB4 by Sanger sequencing. The expression of connexin (Cx) 43 was detected by immunohistochemistry and immunofluorescence (IF) studies in the lesions. Results A 12‐year‐old boy presented with multiple hyperkeratotic plaques on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. A 7‐year‐old girl presented with symmetrical erythematous, plaques on the hands, feet, wrists, and ankles. A novel heterozygous missense mutation c.848C > T (p.P283L) in exon 2 of the GJA1 gene was identified in both patients. A novel heterozygous missense mutation c.869C > A (p.T290N) in exon 2 of the GJA1 gene was also identified in the boy. These mutations were not found in the unaffected family members and 100 normal controls. In the patients’ lesions, Cx43 protein was located to the cytomembrane and cytoplasm in the stratum corneum, and granular layer. Compound heterozygous mutations in the boy showed a more severe clinical phenotype and cytoplasmic mislocalization. Conclusions The novel mutations c.848C > T (p.P283L) and c.869C > A(p.T290N) arose de novo and were considered as the cause of two Chinese EKVP. GJA1 P283L and T290N mutations lead to Cx43 protein cytoplasmic mislocalization. Our finding expands the mutant spectrum of GJA1 gene and adds new understanding of the genotype‐phenotype correlation.https://doi.org/10.1002/mgg3.670Connexins 43Erythrokeratodermia variabilis et progressivaGap junction alpha 1 gene
collection DOAJ
language English
format Article
sources DOAJ
author Changxing Li
Jingyao Liang
Pingjiao Chen
Kang Zeng
Rujun Xue
Xin Tian
Liuping Liang
Qi Wang
Minglan Shi
Xibao Zhang
spellingShingle Changxing Li
Jingyao Liang
Pingjiao Chen
Kang Zeng
Rujun Xue
Xin Tian
Liuping Liang
Qi Wang
Minglan Shi
Xibao Zhang
Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
Molecular Genetics & Genomic Medicine
Connexins 43
Erythrokeratodermia variabilis et progressiva
Gap junction alpha 1 gene
author_facet Changxing Li
Jingyao Liang
Pingjiao Chen
Kang Zeng
Rujun Xue
Xin Tian
Liuping Liang
Qi Wang
Minglan Shi
Xibao Zhang
author_sort Changxing Li
title Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
title_short Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
title_full Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
title_fullStr Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
title_full_unstemmed Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
title_sort two de novo gja1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva
publisher Wiley
series Molecular Genetics & Genomic Medicine
issn 2324-9269
publishDate 2019-06-01
description Abstract Background Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJB4 have been reported to cause EKVP. Here, we report the identification of two de novo missense mutations in the GJA1 gene in two unrelated individuals with EKVP. Methods The patients and his family members were subjected to mutation detection in the candidate gene GJA1, GJB3, and GJB4 by Sanger sequencing. The expression of connexin (Cx) 43 was detected by immunohistochemistry and immunofluorescence (IF) studies in the lesions. Results A 12‐year‐old boy presented with multiple hyperkeratotic plaques on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. A 7‐year‐old girl presented with symmetrical erythematous, plaques on the hands, feet, wrists, and ankles. A novel heterozygous missense mutation c.848C > T (p.P283L) in exon 2 of the GJA1 gene was identified in both patients. A novel heterozygous missense mutation c.869C > A (p.T290N) in exon 2 of the GJA1 gene was also identified in the boy. These mutations were not found in the unaffected family members and 100 normal controls. In the patients’ lesions, Cx43 protein was located to the cytomembrane and cytoplasm in the stratum corneum, and granular layer. Compound heterozygous mutations in the boy showed a more severe clinical phenotype and cytoplasmic mislocalization. Conclusions The novel mutations c.848C > T (p.P283L) and c.869C > A(p.T290N) arose de novo and were considered as the cause of two Chinese EKVP. GJA1 P283L and T290N mutations lead to Cx43 protein cytoplasmic mislocalization. Our finding expands the mutant spectrum of GJA1 gene and adds new understanding of the genotype‐phenotype correlation.
topic Connexins 43
Erythrokeratodermia variabilis et progressiva
Gap junction alpha 1 gene
url https://doi.org/10.1002/mgg3.670
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