{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T06:09:49Z","timestamp":1771049389554,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2020\/37\/B\/NZ5\/03693"],"award-info":[{"award-number":["2020\/37\/B\/NZ5\/03693"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital vertebral malformations (CVMs), affecting approximately 0.5\u20131 per 1000 live births, occur either in an isolated form or as part of syndromic disorders. Despite the identification of numerous causative genes for CVMs, the molecular etiology of most cases remains unknown. In this study, we applied a three-tiered diagnostic approach (chromosomal microarray analysis, followed by custom gene panel analysis, and exome\/genome sequencing) in a cohort of 34 patients with CVMs. We achieved a 12% diagnostic success rate, identifying a deletion upstream of SOX9 and pathogenic or likely pathogenic variants in FLNB and KMT2D. Most pathogenic variants were detected by exome or genome sequencing, while earlier-tier analyses yielded limited results. We also identified two candidate genes, NSD2 and TBXT, that may contribute to the phenotype observed in our patients, but warrant future functional validation. Our work expands the molecular spectrum of CVMs and highlights the utility of comprehensive genomic testing for improving diagnosis and understanding of vertebral development disorders.<\/jats:p>","DOI":"10.3390\/ijms27041752","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:45:36Z","timestamp":1770831936000},"page":"1752","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering the Genetic Basis of Congenital Vertebral Malformations Through a Stepwise Diagnostic Approach"],"prefix":"10.3390","volume":"27","author":[{"given":"Anna","family":"Szoszkiewicz","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Department of Medical Genetics, Doctoral School, Poznan University of Medical Sciences, 61-701 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2493-898X","authenticated-orcid":false,"given":"Anna","family":"Sowi\u0144ska-Seidler","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Wnuk-K\u0142osi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Department of Medical Genetics, Doctoral School, Poznan University of Medical Sciences, 61-701 Poznan, Poland"},{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ewelina","family":"Bukowska-Olech","sequence":"additional","affiliation":[{"name":"Department of Laboratory Diagnostics, Poznan University of Medical Sciences, 60-569 Poznan, Poland"},{"name":"University Clinical Hospital in Pozna\u0144, 60-786 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Biel","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karolina","family":"Matuszewska","sequence":"additional","affiliation":[{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcin","family":"Biel","sequence":"additional","affiliation":[{"name":"Department of Radiology, HCP Medical Center Poznan, 61-485 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Badura-Stronka","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Glazar","sequence":"additional","affiliation":[{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Jakubiuk-Tomaszuk","sequence":"additional","affiliation":[{"name":"Department of Neurology and Pediatrics, Medical University of Bialystok, 15-274 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4268-7707","authenticated-orcid":false,"given":"Maciej","family":"Krawczy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-646X","authenticated-orcid":false,"given":"Krzysztof","family":"Szcza\u0142uba","sequence":"additional","affiliation":[{"name":"Center of Excellence for Rare and Undiagnosed Disorders, Medical University of Warsaw, 02-091 Warsaw, Poland"},{"name":"Department of Medical Genetics, Medical University of Warsaw, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-4572","authenticated-orcid":false,"given":"Karolina","family":"\u015aledzi\u0144ska","sequence":"additional","affiliation":[{"name":"Department and Clinics of Pediatrics, Hematology and Oncology, Medical University of Gdansk, 80-952 Gdansk, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzena","family":"Wi\u015bniewska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4058-3901","authenticated-orcid":false,"given":"Aleksander","family":"Jamsheer","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Poznan University of Medical Sciences, 60-806 Poznan, Poland"},{"name":"Diagnostyka GENESIS, 60-529 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1136\/jmedgenet-2015-103554","article-title":"The genetic landscape and clinical implications of vertebral anomalies in VACTERL association","volume":"53","author":"Chen","year":"2016","journal-title":"J. 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