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.
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Acknowledgements
We thank the individuals who participated in this project, and the patients in this study who provided written informed consent for the publication of their case details. This study was funded by Anhui Provincial Quality Engineering Project of Higher Education Institutions (No. 2020jyxm0922), Natural Science Research Project of Higher Education Department of Anhui Province (No. KJ2021A0284), Fund of Anhui Provincial Institute of Translational Medicine (No.2021zhyx-C31), and Research Foundation of Anhui Medical University (No. 2020xkj154).
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Hequn Huang, Mengyun Chen, Xia Liu, Xixi Xiong, Lanbo Zhou, Zhonglan Su, Yan Lu, and Bo Liang declare that they have no conflicts of interest. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for inclusion in the study.
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Huang, H., Chen, M., Liu, X. et al. A novel variant in the GJB6 gene in a large Chinese family with a unique phenotype of Clouston syndrome. Front. Med. 17, 330–338 (2023). https://doi.org/10.1007/s11684-022-0933-2
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DOI: https://doi.org/10.1007/s11684-022-0933-2