{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T14:56:38Z","timestamp":1758812198578,"version":"3.37.3"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T00:00:00Z","timestamp":1435622400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"BONFOR"},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","award":["DFG; BE 2346\/4-2"],"award-info":[{"award-number":["DFG; BE 2346\/4-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Three children from an expanded consanguineous Kuwaiti kindred presented with ankyloblepharon, sparse and curly hair, and hypoplastic nails, suggestive of CHAND syndrome (OMIM 214350) that belongs to the heterogeneous spectrum of ectodermal dysplasias. After exclusion of pathogenic mutations in TP63 we performed homozygosity mapping, followed by exome sequencing of one affected individual. We initially identified three homozygous mutations in the linked region, located in PWP2, MX2 and RIPK4. Recently, mutations in RIPK4 have been reported in Bartsocas\u2010Papas syndrome (OMIM 263650) that shows overlapping clinical symptoms with the phenotype observed in the affected individuals studied here. Subsequent analysis of affected and non\u2010affected family members showed that mutation c.850G&gt;A (p.Glu284Lys) in RIPK4 was in complete segregation with the disease phenotype, in accordance with an autosomal recessive inheritance pattern, thus supporting pathogenicity of this variant. Interestingly, however, our patients did not have cleft lip\/palate, a common feature encountered in Bartsocas\u2010Papas syndrome. Whereas in Bartsocas\u2010Papas syndromes missense mutations are usually located within the serin\/threonin kinase of RIPK4, the mutation detected in our family resides just outside of the kinase domain, which could explain the milder phenotype. Our data raise the question if CHAND syndrome indeed is a distinct entity. Alternatively, CHAND and Bartsocas\u2010Papas syndrome might be allelic disorders or RIPK4 mutations could confer varying degrees of phenotypic severity, depending on their localization within or outside functionally important domains. Our findings indicate that making an accurate diagnosis based only on the prevailing clinical symptoms is challenging. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37233","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T12:17:04Z","timestamp":1435666624000},"page":"2555-2562","source":"Crossref","is-referenced-by-count":12,"title":["Identification of a novel mutation in <i>RIPK4<\/i> in a kindred with phenotypic features of Bartsocas\u2010Papas and CHAND syndromes"],"prefix":"10.1002","volume":"167","author":[{"given":"Benjamin","family":"Gollasch","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fitnat Buket","family":"Basmanav","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arti","family":"Nanda","sequence":"additional","affiliation":[{"name":"Genetic Skin Diseases Clinic As'ad Al\u2010Hamad Dermatology Center Al\u2010Sabah Hospital Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcnter","family":"Fritz","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Neurozentrum University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hassnaa","family":"Mahmoudi","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Wehner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Wolf","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine","family":"Altm\u00fcller","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne Cologne Germany"},{"name":"Institute of Human Genetics University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Cologne Center for Genomics (CCG) University of Cologne Cologne Germany"},{"name":"Cluster of Excellence on Cellular Stress Responses in Aging\u2010Associated Diseases (CECAD) University of Cologne Cologne Germany"},{"name":"Center for Molecular Medicine Cologne (CMMC) University of Cologne Cologne Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Frank","sequence":"additional","affiliation":[{"name":"Division of Dermatogenetics and Skin Cancer Center Department of Dermatology University of D\u00fcsseldorf D\u00fcsseldorf Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina C.","family":"Betz","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of Bonn Bonn Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2009.10.006"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700588"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.12.003"},{"key":"e_1_2_6_5_1","first-page":"100","article-title":"CHANDS: The curly hair\u2010ankyloblepharon\u2010nail dysplasia syndrome","volume":"7","author":"Baughman FA","year":"1971","journal-title":"Birth Defects Orig Artic 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Ankyloblepharon\u2010ectodermal defects\u2010cleft lip\/palate syndrome. In: Genereviews at genetests: Medical genetics information resource [database online]. 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