{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T08:12:49Z","timestamp":1768983169220,"version":"3.49.0"},"reference-count":19,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Bothnian palmoplantar keratoderma (PPKB, MIM600231) is an autosomal dominant form of diffuse non-epidermolytic PPK characterized by spontaneous yellowish-white PPK associated with a spongy appearance after water-immersion. It is due to AQP5 heterozygous mutations. We report four patients carrying a novel AQP5 heterozygous mutation (c.125T&gt;A; p.(Ile42Asn)), and belonging to the same French family. Early palmoplantar swelling (before one year of age), pruritus and hyperhidrosis were constant. The PPK was finally characterized as transgrediens, non-progrediens, diffuse PPK with a clear delineation between normal and affected skin. The cutaneous modifications at water-immersion test, \u201chand-in-the-bucket sign\u201d, were significantly evident after 3 to 6 min of immersion in the children and father, respectively. AQP5 protein is expressed in eccrine sweat glands (ESG), salivary and airway submucosal glands. In PPKB, gain of function mutations seem to widen the channel diameter of ESG and increase water movement. Thus, swelling seems to be induced by hypotonicity with water entrance into cells, while hyperhidrosis is the result of an increased cytosolic calcium concentration.<\/jats:p>","DOI":"10.3390\/genes13122360","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T02:20:57Z","timestamp":1671070857000},"page":"2360","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Bothnian Palmoplantar Keratoderma: Further Delineation of the Associated Phenotype"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3528-9804","authenticated-orcid":false,"given":"Laura","family":"Fertitta","sequence":"first","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 149 rue de S\u00e8vres\u201475743 PARIS, CEDEX 15, 75679 Paris, France"},{"name":"Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabienne","family":"Charbit-Henrion","sequence":"additional","affiliation":[{"name":"INSERM U1163, Institut Imagine, H\u00f4pital Universitaire Necker-Enfants Malades, 75015 Paris, France"},{"name":"Genomic Medecine Unit, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2468-3910","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Leclerc-Mercier","sequence":"additional","affiliation":[{"name":"Department of Pathology, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3738-7299","authenticated-orcid":false,"given":"Thao","family":"Nguyen-Khoa","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"},{"name":"Reference Center for Rare Diseases: Cystic Fibrosis and Other Epithelial Respiratory Protein Misfolding Diseases, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"},{"name":"INSERM U1151, Institut Necker-Enfants Malades, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Baran","sequence":"additional","affiliation":[{"name":"Nail Disease Center, 06400 Cannes, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Alby","sequence":"additional","affiliation":[{"name":"Genomic Medecine Unit, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Steffann","sequence":"additional","affiliation":[{"name":"INSERM U1163, Institut Imagine, H\u00f4pital Universitaire Necker-Enfants Malades, 75015 Paris, France"},{"name":"Genomic Medecine Unit, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Sermet-Gaudelus","sequence":"additional","affiliation":[{"name":"Reference Center for Rare Diseases: Cystic Fibrosis and Other Epithelial Respiratory Protein Misfolding Diseases, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"},{"name":"INSERM U1151, Institut Necker-Enfants Malades, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smail","family":"Hadj-Rabia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 149 rue de S\u00e8vres\u201475743 PARIS, CEDEX 15, 75679 Paris, France"},{"name":"Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), H\u00f4pital Necker-Enfants Malades, AP-HP Centre Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"},{"name":"INSERM U1163, Institut Imagine, H\u00f4pital Universitaire Necker-Enfants Malades, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1093\/hmg\/3.10.1789","article-title":"The gene for diffuse palmoplantar keratoderma of the type found in northern Sweden is localized to chromosome 12q11-q13","volume":"3","author":"Lind","year":"1994","journal-title":"Hum. 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