{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:03:41Z","timestamp":1780495421844,"version":"3.54.1"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,6,28]],"date-time":"2024-06-28T00:00:00Z","timestamp":1719532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["310030_200354"],"award-info":[{"award-number":["310030_200354"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Hypohidrotic ectodermal dysplasia is a developmental defect characterized by sparse or absent hair, missing or malformed teeth and defects in eccrine glands. Loss-of-function variants in the X-chromosomal EDA gene have been reported to cause hypohidrotic ectodermal dysplasia in humans, mice, dogs and cattle. We investigated a male cat exhibiting diffuse truncal alopecia with a completely absent undercoat. The cat lacked several teeth, and the remaining teeth had an abnormal conical shape. Whole-genome sequencing revealed a hemizygous missense variant in the EDA gene, XM_011291781.3:c.1042G&gt;A or XP_011290083.1:p.(Ala348Thr). The predicted amino acid exchange is located in the C-terminal TNF signaling domain of the encoded ectodysplasin. The corresponding missense variant in the human EDA gene, p.Ala349Thr, has been reported as a recurring pathogenic variant in several human patients with X-linked hypohidrotic ectodermal dysplasia. The identified feline variant therefore represents the likely cause of the hypohidrotic ectodermal dysplasia in the investigated cat, and the genetic investigation confirmed the suspected clinical diagnosis. This is the first report of an EDA-related hypohidrotic ectodermal dysplasia in cats.<\/jats:p>","DOI":"10.3390\/genes15070854","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T06:04:18Z","timestamp":1719986658000},"page":"854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["EDA Missense Variant in a Cat with X-Linked Hypohidrotic Ectodermal Dysplasia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0932-552X","authenticated-orcid":false,"given":"Stefan J.","family":"Rietmann","sequence":"first","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"},{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00eblle","family":"Cochet-Faivre","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Dermatologie, CHUV-Animaux de Compagnie, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94700 Maisons-Alfort, France"},{"name":"BIPAR, Laboratoire de Sant\u00e9 Animale, INRAE, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Dropsy","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Dermatologie, CHUV-Animaux de Compagnie, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vidhya","family":"Jagannathan","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8602-1993","authenticated-orcid":false,"given":"Lucie","family":"Chevallier","sequence":"additional","affiliation":[{"name":"U955-IMRB, Team 10-Biology of the Neuromuscular System, INSERM, UPEC, Ecole Nationale V\u00e9t\u00e9rinaire d\u2019Alfort, 94700 Maisons-Alfort, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0553-4880","authenticated-orcid":false,"given":"Tosso","family":"Leeb","sequence":"additional","affiliation":[{"name":"Institute of Genetics, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland"},{"name":"Dermfocus, University of Bern, 3001 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,28]]},"reference":[{"key":"ref_1","unstructured":"Darwin, C.R. (1875). The Variation of Animals and Plants under Domestication, John Murray. [2nd ed.]. Chapter XXV."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1111\/ijd.14048","article-title":"Hypohidrotic ectodermal dysplasia: Clinical and molecular review","volume":"57","year":"2018","journal-title":"Int. J. Dermatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/ajmg.a.61045","article-title":"Ectodermal dysplasias: Classification and organization by phenotype, genotype and molecular pathway","volume":"179","author":"Wright","year":"2019","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/ng0895-409","article-title":"X-linked anhidrotic (hypohidrotic) ectodermal dysplasia is caused by mutation in a novel transmembrane protein","volume":"13","author":"Kere","year":"1996","journal-title":"Nat. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1093\/hmg\/6.9.1589","article-title":"Cloning of Tabby, the murine homolog of the human EDA gene: Evidence for a membrane-associated protein with a short collagenous domain","volume":"6","author":"Ferguson","year":"1997","journal-title":"Hum. Mol. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13069","DOI":"10.1073\/pnas.94.24.13069","article-title":"The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains","volume":"94","author":"Srivastava","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1086\/301984","article-title":"Identification of a new splice form of the EDA1 gene permits detection of nearly all X-linked hypohidrotic ectodermal dysplasia mutations","volume":"63","author":"Monreal","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1126\/science.290.5491.523","article-title":"Two-amino acid molecular switch in an epithelial morphogen that regulates binding to two distinct receptors","volume":"290","author":"Yan","year":"2000","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1002\/ajmg.a.32855","article-title":"Molecular aspects of hypohidrotic ectodermal dysplasia","volume":"149A","author":"Mikkola","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/11937","article-title":"Mutations in the human homologue of mouse dl cause autosomal recessive and dominant hypohidrotic ectodermal dysplasia","volume":"22","author":"Monreal","year":"1999","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1038\/414913a","article-title":"Gene defect in ectodermal dysplasia implicates a death domain adapter in development","volume":"414","author":"Headon","year":"2001","journal-title":"Nature"},{"key":"ref_12","unstructured":"(2024, April 04). LOVD v3.0 Build 29. Available online: https:\/\/databases.lovd.nl\/shared\/genes\/EDA."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s00335-004-2463-4","article-title":"Mutation identification in a canine model of X-linked ectodermal dysplasia","volume":"16","author":"Casal","year":"2005","journal-title":"Mamm. Genome"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1534\/g3.116.033225","article-title":"A splice defect in the EDA gene in dogs with an X-linked hypohidrotic ectodermal dysplasia (XLHED) phenotype","volume":"6","author":"Waluk","year":"2016","journal-title":"G3 Genes Genomes Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1111\/age.12729","article-title":"A frameshift variant in the EDA gene in Dachshunds with X-linked hypohidrotic ectodermal dysplasia","volume":"49","author":"Bauer","year":"2018","journal-title":"Anim. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1534\/g3.118.200814","article-title":"A de novo EDA-variant in a litter of shorthaired standard Dachshunds with X-linked hypohidrotic ectodermal dysplasia","volume":"9","author":"Vasiliadis","year":"2019","journal-title":"G3 Genes Genomes Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1101\/gr.182501","article-title":"Partial deletion of the bovine ED1 gene causes anhidrotic ectodermal dysplasia in cattle","volume":"11","author":"Distl","year":"2001","journal-title":"Genome Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s00109-002-0320-z","article-title":"A single point mutation within the ED1 gene disrupts correct splicing at two different splice sites and leads to anhidrotic ectodermal dysplasia in cattle","volume":"80","author":"Peters","year":"2002","journal-title":"J. Mol. Med."},{"key":"ref_19","first-page":"612","article-title":"Congenital hypotrichosis and partial anodontia in a crossbred beef calf","volume":"48","author":"Barlund","year":"2007","journal-title":"Can. Vet. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/j.1601-5223.2010.02202.x","article-title":"A novel mutation of the bovine EDA gene associated with anhidrotic ectodermal dysplasia in Holstein cattle","volume":"148","author":"Ogino","year":"2011","journal-title":"Hereditas"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1111\/j.1365-2052.2011.02192.x","article-title":"Exonization of a LINE1 fragment implicated in X-linked hypohidrotic ectodermal dysplasia in cattle","volume":"42","author":"Cirera","year":"2011","journal-title":"Anim. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gargani, M., Valentini, A., and Pariset, L. (2011). A novel point mutation within the EDA gene causes an exon dropping in mature RNA in Holstein Friesian cattle breed affected by X-linked anhidrotic ectodermal dysplasia. BMC Vet. Res., 7.","DOI":"10.1186\/1746-6148-7-35"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/j.1365-2052.2011.02290.x","article-title":"De novo mutation of the bovine EDA gene associated with anhidrotic ectodermal dysplasia in Japanese Black cattle","volume":"43","author":"Ogino","year":"2012","journal-title":"Anim. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Escouflaire, C., Rebours, E., Charles, M., Orellana, S., Cano, M., Rivi\u00e8re, J., Grohs, C., Hayes, H., and Capitan, A. (2019). A de novo 3.8-Mb inversion affecting the EDA and XIST genes in a heterozygous female calf with generalized hypohidrotic ectodermal dysplasia. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6087-1"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"O\u2019Toole, D., H\u00e4fliger, I.M., Leuthard, F., Schumaker, B., Steadman, L., Murphy, B., Dr\u00f6gem\u00fcller, C., and Leeb, T. (2021). X-linked hypohidrotic ectodermal dysplasia in crossbred beef cattle due to a large deletion in EDA. Animals, 11.","DOI":"10.3390\/ani11030657"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13028-022-00641-2","article-title":"A large deletion encompassing exon 2 of the ectodysplasin A (EDA) gene in a British blue crossbred calf with hypohidrotic ectodermal dysplasia","volume":"64","author":"Capuzzello","year":"2022","journal-title":"Acta Vet. Scand."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Reinartz, S., Wei\u00df, C., Heppelmann, M., Hewicker-Trautwein, M., Hellige, M., Willen, L., Feige, K., Schneider, P., and Distl, O. (2023). A missense mutation in the collagen triple helix of EDA is associated with X-linked recessive hypohidrotic ectodermal dysplasia in Fleckvieh cattle. Genes, 15.","DOI":"10.3390\/genes15010008"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Krull, F., Bleyer, M., Sch\u00e4fer, J., and Brenig, B. (2024). A missense mutation in the highly conserved TNF-like domain of ectodysplasin A is the candidate causative variant for X-linked hypohidrotic ectodermal dysplasia in Limousin cattle: Clinical, histological, and molecular analyses. PLoS ONE, 19.","DOI":"10.1371\/journal.pone.0291411"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1086\/521988","article-title":"Significant correction of disease after postnatal administration of recombinant ectodysplasin A in canine X-linked ectodermal dysplasia","volume":"81","author":"Casal","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1056\/NEJMoa1714322","article-title":"Prenatal correction of X-linked hypohidrotic ectodermal dysplasia","volume":"378","author":"Schneider","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/age.12834","article-title":"A Comprehensive Biomedical Variant Catalogue Based on Whole Genome Sequences of 582 Dogs and Eight Wolves","volume":"50","author":"Jagannathan","year":"2019","journal-title":"Anim. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A Program for Annotating and Predicting the Effects of Single Nucleotide Polymorphisms, SnpEff","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bendl, J., Stourac, J., Salanda, O., Pavelka, A., Wieben, E.D., Zendulka, J., Brezovsky, J., and Damborsky, J. (2014). PredictSNP: Robust and accurate consensus classifier for prediction of disease-related mutations. PLoS Comput. Biol., 10.","DOI":"10.1371\/journal.pcbi.1003440"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5918","DOI":"10.1038\/s41467-020-19669-x","article-title":"Inferring the molecular and phenotypic impact of amino acid variants with MutPred2","volume":"11","author":"Pejaver","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_36","unstructured":"(2024, April 18). Mol* 3D Viewer. Available online: https:\/\/www.rcsb.org\/3d-view."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/j.str.2003.11.009","article-title":"The crystal structures of EDA-A1 and EDA-A2: Splice variants with distinct receptor specificity","volume":"11","author":"Hymowitz","year":"2003","journal-title":"Structure"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1111\/j.1365-3164.2004.00407.x","article-title":"Clinical and genetic aspects of X-linked ectodermal dysplasia in the dog\u2014A review including three new spontaneous cases","volume":"15","author":"Moura","year":"2004","journal-title":"Vet. Dermatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1601-6343.2009.01473.x","article-title":"Dental abnormalities associated with X-linked hypohidrotic ectodermal dysplasia in dogs","volume":"13","author":"Lewis","year":"2010","journal-title":"Orthod. Craniofac. Res."},{"key":"ref_40","unstructured":"(2024, April 18). 99 Lives. Available online: https:\/\/cvm.missouri.edu\/research\/feline-genetics-and-comparative-medicine-laboratory\/99-lives\/."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1111\/jvim.16805","article-title":"Precision medicine using whole genome sequencing in a cat identifies a novel COL5A1 variant for classical Ehlers-Danlos syndrome","volume":"37","author":"McElroy","year":"2023","journal-title":"J. Vet. Intern. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1093\/hmg\/7.11.1661","article-title":"The anhidrotic ectodermal dysplasia gene (EDA) undergoes alternative splicing and encodes ectodysplasin-A with deletion mutations in collagenous repeats","volume":"7","author":"Hartung","year":"1998","journal-title":"Hum. Mol. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1111\/j.1399-0004.2008.01037.x","article-title":"X-linked hypohidrotic ectodermal dysplasia. Genetic and dental findings in 67 Danish patients from 19 families","volume":"74","author":"Lexner","year":"2008","journal-title":"Clin. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1097\/00005537-200206000-00005","article-title":"Ectodermal dysplasia: Otolaryngologic manifestations and management","volume":"112","author":"Daniel","year":"2002","journal-title":"Laryngoscope"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.jcpa.2004.11.001","article-title":"Ectodysplasin-1 deficiency in a German Holstein bull associated with loss of respiratory mucous glands and chronic rhinotracheitis","volume":"132","author":"Seeliger","year":"2005","journal-title":"J. Comp. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/BF00276326","article-title":"The mutational spectrum of single base-pair substitutions causing human genetic disease: Patterns and predictions","volume":"85","author":"Cooper","year":"1990","journal-title":"Hum. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/7\/854\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:07:08Z","timestamp":1760108828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/7\/854"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,28]]},"references-count":46,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["genes15070854"],"URL":"https:\/\/doi.org\/10.3390\/genes15070854","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,28]]}}}