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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

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Frontiers of Medicine  2023, Vol. 17 Issue (2): 330-338   https://doi.org/10.1007/s11684-022-0933-2
  本期目录
A novel variant in the GJB6 gene in a large Chinese family with a unique phenotype of Clouston syndrome
Hequn Huang1,2,3, Mengyun Chen1,2,3, Xia Liu4, Xixi Xiong5, Lanbo Zhou5, Zhonglan Su5, Yan Lu5(), Bo Liang1,2,3,6()
1. Institute of Dermatology and Department of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei 230000, China
2. Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei 230000, China
3. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei 230000, China
4. Huai’an District Skin Disease Prevention and Treatment Hospital, Huai’an 223000, China
5. Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
6. Department of Clinical Laboratory, The First Affiliated Hospital, Anhui Medical University, Hefei 230000, China
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Abstract：

Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients’ hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.
Key words： Clouston syndrome    whole exome sequencing    GJB6 gene    novel variant    unique phenotype
收稿日期: 2021-11-10      出版日期: 2023-05-26
Corresponding Author(s): Yan Lu,Bo Liang   
 引用本文:   
. [J]. Frontiers of Medicine, 2023, 17(2): 330-338.
Hequn Huang, Mengyun Chen, Xia Liu, Xixi Xiong, Lanbo Zhou, Zhonglan Su, Yan Lu, Bo Liang. A novel variant in the GJB6 gene in a large Chinese family with a unique phenotype of Clouston syndrome. Front. Med., 2023, 17(2): 330-338.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-022-0933-2
https://academic.hep.com.cn/fmd/CN/Y2023/V17/I2/330
Fig.1  
Numbera Age (year) Sex Alopecia Eyebrows/eyelashes/body hair Nails Palmoplantar keratosis Nail pain
II:2 90–95 M – – + – +
II:4 90–95 F – – + – +
III:3 70–75 F +– – + – +
III:6 60–65 M +– – + – +
III:8 60–65 F +– – + – +
III:11 50–55 M +– + + + +
III:15 50–55 F – – + – +
IV:5 50–55 M + + + + +
IV:7 40–45 F – – + – +
IV:11 30–35 F +– + + – +
IV:13 30–35 F +– – + – +
IV:15 30–35 M +– – + – +
IV:17 40–45 F – – + – +
IV:19 30–35 M + + + + +
V:1 20–25 M + + + + +
V:2 15–20 M – – + – +
V:3 10–15 F – – + – +
V:6 10–15 M + + + – +
V:8 5–10 F + + + – +
V:10 10–15 F + + + – +
V:11 0–5 F + + + – +
Tab.1  
Fig.2  
Fig.3  
Fig.4  
Fig.5  
Fig.6  
No. Nucleotide and amino acid change of GJB6 gene Mutation type Protein domain Ethnic group MAF gnomAD-total population MAF gnomAD-patient’s ethnicity population Eyes phenotype Clubbed digits Reference
1 c.31G > A.(G11R) Missense N-terminal in cytoplasm French 3.99E–06 8.85E–06 / / Lamartine et al., 2000 [7]
2 Missense Dutch 8.85E–06 / / Maurice et al., 2003 [24]
3 Missense Chinese 0 / / Zhang et al., 2003 [2]
4 Missense Chinese 0 / / Chen et al., 2010 [18]
5 Missense German 8.85E–06 / / Fujimoto et al., 2013 [12]
6 Missense Chinese 0 / / Mousumi et al., 2013 [25]
7 Missense Chinese 0 / / Qiao et al., 2016 [26]
8 Missense / / / Odell et al., 2016 [27]
9 Missense Indian 0 / / Agarwal et al., 2016 [28]
10 Missense Chinese 0 / / Hu et al., 2015 [29]
11 c.263C > T.(A88V) Missense M2 domain in plasma membrane India, Malaysia, and Wales / / / / Lamartine et al., 2000 [7]
13 Missense Chinese / / / / Yang et al., 2016 [17]
14 Missense Venezuelan / / / / Cammarata-Scalisi et al., 2019 [30]
15 Missense Russian / / / / Marakhonov et al., 2012 [31]
16 c.148G > A.(D50N) Missense E1 domain in extracellular loops Ashkenazi Jews / / / / BARIS et al., 2008 [9]
17 c.110T > A.(V37E) Missense M1 domain in plasma membrane Scottish 3.98E–06 0 / / Frances et al., 2002 [8]
Tab.2  
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