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Alterations of different genes of this network may result in overlapping phenotypes, as exemplified by disorders due to the impairment of the parathyroid hormone\/parathyroid hormone-related protein pathway, and obtaining a correct diagnosis is sometimes challenging without a genetic confirmation. Five patients with Albright's hereditary osteodystrophy (AHO)-like skeletal malformations without a clear clinical diagnosis were analyzed by whole-exome sequencing (WES) and novel potentially pathogenic variants in parathyroid hormone like hormone (PTHLH) (BDE with short stature [BDE2]) and TRPS1 (tricho-rhino-phalangeal syndrome [TRPS]) were discovered. The pathogenic impact of these variants was confirmed by in vitro functional studies. This study expands the spectrum of genetic defects associated with BDE2 and TRPS and demonstrates the pathogenicity of TRPS1 missense variants located outside both the nuclear localization signal and the GATA ((A\/T)GATA(A\/G)-binding zinc-containing domain) and Ikaros-like binding domains. Unfortunately, we could not find distinctive phenotypic features that might have led to an earlier clinical diagnosis, further highlighting the high degree of overlap among skeletal syndromes associated with brachydactyly and AHO-like features, and the need for a close interdisciplinary workout in these rare patients. \u00a9 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4490","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T02:10:43Z","timestamp":1639361443000},"page":"465-474","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Novel Pathogenetic Variants in PTHLH and TRPS1 Genes Causing Syndromic Brachydactyly"],"prefix":"10.1093","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-3843","authenticated-orcid":false,"given":"Francesca Marta","family":"Elli","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah","family":"Mattinzoli","sequence":"additional","affiliation":[{"name":"Renal Research Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Lucca","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Piu","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria A.","family":"Maffini","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jole","family":"Costanza","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UOS Coordinamento Laboratori di Ricerca, Direzione Scientifica Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fontana","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UOS Coordinamento Laboratori di Ricerca, Direzione Scientifica Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Santaniello","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, UOS Coordinamento Laboratori di Ricerca, Direzione Scientifica Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Forino","sequence":"additional","affiliation":[{"name":"UO Pediatria, Fondazione Poliambulanza Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatella","family":"Milani","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Unit\u00e0 di Pediatria Alta Intensit\u00e0 di Cura Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Teresa","family":"Bonati","sequence":"additional","affiliation":[{"name":"Clinic of Medical Genetics, IRCCS Istituto Auxologico Italiano Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Secco","sequence":"additional","affiliation":[{"name":"SC Pediatria e DEA Pediatrico, Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo Alessandria Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gastaldi","sequence":"additional","affiliation":[{"name":"Clinica Pediatrica IRCCS Giannina Gaslini Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Dialysis and Renal Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"},{"name":"Department of Clinical Sciences and Community Health University of Milan Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Messa","sequence":"additional","affiliation":[{"name":"Dialysis and Renal Transplant Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy"},{"name":"Department of Clinical Sciences and Community Health University of Milan Milan 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