{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:39:23Z","timestamp":1792726763435,"version":"4.5.0"},"reference-count":18,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>KRT17<\/jats:italic>\n                    \u2010pEDD (formerly pachyonychia congenita Type 2) is a rare autosomal dominant palmoplantar epidermal differentiation disorder caused by pathogenic variants in the\n                    <jats:italic>KRT17<\/jats:italic>\n                    gene. Most variants cluster within highly conserved helix boundary motifs essential for keratin filament assembly. This multicenter registry\u2010based study evaluated genotype\u2013phenotype correlations among three\n                    <jats:italic>KRT17<\/jats:italic>\n                    codon 88 substitutions: p.(Met88Lys), p.(Met88Arg), and p.(Met88Thr). Sixteen affected individuals from eight unrelated families across eight countries were identified through the International Pachyonychia Congenita Research Registry. Clinical data were collected using standardized questionnaires and medical record review. A genotype\u2013phenotype correlation was observed according to substitution properties. Charged substitutions (lysine and arginine) were associated with earlier onset and more severe disease, including marked hypertrophic nail dystrophy and painful plantar keratoderma frequently requiring treatment. Persistent hoarseness was noted in all three p.(Met88Arg) carriers, a preliminary finding that may suggest a broader phenotypic spectrum in\n                    <jats:italic>KRT17<\/jats:italic>\n                    \u2010pEDD pending confirmation in larger cohorts, while natal teeth showed complete penetrance in the p.(Met88Lys) group. In contrast, p.(Met88Thr) was associated with a milder and more variable clinical course. Cutaneous adnexal manifestations were common across all groups. These findings identify codon 88 as a structurally sensitive functional hotspot in\n                    <jats:italic>KRT17<\/jats:italic>\n                    , where the physicochemical nature of the amino acid substitution may influence clinical severity. The results refine clinical interpretation of\n                    <jats:italic>KRT17\u2010<\/jats:italic>\n                    pEDD and support improved counseling and future pathogenesis\u2010based precision therapies.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70336","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:13:58Z","timestamp":1792725238000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotype\u2013Phenotype Correlations in\n                    <scp>\n                      <i>KRT17<\/i>\n                    <\/scp>\n                    \u2010\n                    <scp>PEDD<\/scp>\n                    : The Critical Role of Codon 88"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8489-0044","authenticated-orcid":false,"given":"Hande Nur Cesur","family":"Baltac\u0131","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Ankara University School of Medicine  Ankara Turkey"},{"name":"Department of Medical Genetics Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2732-9132","authenticated-orcid":false,"given":"Merve Ayg\u00fcn","family":"Alizada","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ankara University School of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe","family":"Boyvat","sequence":"additional","affiliation":[{"name":"Department of Dermatology Ankara University School of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halil G\u00fcrhan","family":"Karabulut","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Ankara University School of Medicine  Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"issue":"3","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/ng0795-363","article-title":"Mutation of a Type II Keratin Gene (K6a) in Pachyonychia Congenita","volume":"10","author":"Bowden P. E.","year":"1995","journal-title":"Nature Genetics"},{"issue":"4","key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.jaad.2011.12.009","article-title":"A Review of the Clinical Phenotype of 254 Patients With Genetically Confirmed Pachyonychia Congenita","volume":"67","author":"Eliason M. J.","year":"2012","journal-title":"Journal of the American Academy of Dermatology"},{"issue":"5","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/jid.2010.373","article-title":"Genotype\u2013Phenotype Correlations Among Pachyonychia Congenita Patients With K16 Mutations","volume":"131","author":"Fu T.","year":"2011","journal-title":"Journal of Investigative Dermatology"},{"key":"e_1_2_10_5_1","unstructured":"International Pachyonychia Congenita Research Registry. n.d.\u201cPC Data. Pachyonychia Congenita Project\u201d.https:\/\/www.pachyonychia.org\/pc\u2010data\/."},{"issue":"1","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1111\/j.1469-1809.1951.tb02468.x","article-title":"Pachyonychia Congenita: A Report of Six Cases in One Family: With a Note on Linkage Data","volume":"16","author":"Jackson A.","year":"1951","journal-title":"Annals of Eugenics"},{"key":"e_1_2_10_7_1","first-page":"29","volume-title":"Ikonographia Dermatologica","author":"Jadassohn J.","year":"1906"},{"issue":"3","key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1111\/j.1600-0625.2009.01006.x","article-title":"Expression of Keratins in Cutaneous Epithelial Tumors and Related Disorders\u2013Distribution and Clinical Significance","volume":"20","author":"Kurokawa I.","year":"2011","journal-title":"Experimental Dermatology"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1087\u20100024.2005.10202.x"},{"issue":"3","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/ng0395-273","article-title":"Keratin 16 and Keratin 17 Mutations Cause Pachyonychia Congenita","volume":"9","author":"McLean W.","year":"1995","journal-title":"Nature Genetics"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1087-0024.2005.10205.x","article-title":"Insights Into Genotype\u2013Phenotype Correlation in Pachyonychia Congenita From the Human Intermediate Filament Mutation Database","volume":"10","author":"McLean W. I.","year":"2005","journal-title":"Journal of Investigative Dermatology. Symposium Proceedings"},{"issue":"6","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1007\/s00418-008-0435-6","article-title":"The Human Keratins: Biology and Pathology","volume":"129","author":"Moll R.","year":"2008","journal-title":"Histochemistry and Cell Biology"},{"issue":"5","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards S.","year":"2015","journal-title":"Genetics in Medicine"},{"issue":"3","key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1111\/bjd.18794","article-title":"Revisiting Pachyonychia Congenita: A Case\u2010Cohort Study of 815 Patients","volume":"182","author":"Samuelov L.","year":"2020","journal-title":"British Journal of Dermatology"},{"issue":"2","key":"e_1_2_10_15_1","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1001\/jamadermatol.2013.6448","article-title":"Pachyonychia Congenita in Pediatric Patients: Natural History, Features, and Impact","volume":"150","author":"Shah S.","year":"2014","journal-title":"JAMA Dermatology"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1087\u20100024.2005.10204.x"},{"issue":"3","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1093\/bjd\/ljaf054","article-title":"Palmoplantar Epidermal Differentiation Disorders: A New Classification Toward Pathogenesis Based Therapy","volume":"193","author":"Sprecher E.","year":"2025","journal-title":"British Journal of Dermatology"},{"issue":"11","key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1110\/ps.8.11.2312","article-title":"The Role of Position a in Determining the Stability and Oligomerization State of \u03b1\u2010Helical Coiled Coils: 20 Amino Acid Stability Coefficients in the Hydrophobic Core of Proteins","volume":"8","author":"Wagschal K.","year":"1999","journal-title":"Protein Science"},{"issue":"2","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/bjd.12958","article-title":"The Molecular Genetic Analysis of the Expanding Pachyonychia Congenita Case Collection","volume":"171","author":"Wilson N.","year":"2014","journal-title":"British Journal of Dermatology"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70336","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.70336","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.70336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:14:06Z","timestamp":1792725246000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.70336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":18,"alternative-id":["10.1002\/ajmg.a.70336"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.70336","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]},"assertion":[{"value":"2026-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajmg.a.70336"}}