{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T13:54:39Z","timestamp":1761746079689,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and Higher Education of the Russian Federation","award":["RF 193021X0029"],"award-info":[{"award-number":["RF 193021X0029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Introduction: Pathogenic variants in the OFD1 gene are linked to a spectrum of syndromes that exhibit partial clinical overlap. Hemizygous loss-of-function variants are considered lethal in males, while heterozygous loss-of-function variants generally result in oro-facial-digital syndrome type 1. A reported phenotype, Simpson\u2013Golabi\u2013Behmel syndrome type 2, was published once but remains controversial, with many specialists questioning its validity and arguing about its continued listing in the OMIM database. Methods: To investigate the genetic and phenotypic characteristics of the patients, we performed clinical exome sequencing, family-based genetic analysis, X-inactivation studies, electron microscopy, and detailed clinical assessments. Results: Three patients from unrelated families carrying loss-of-function variants in the OFD1 gene were identified, emphasizing the diverse phenotypic spectrum of OFD1-associated disorders. The first patient, a female with a heterozygous frameshift variant p.(Gln398LeufsTer2), was diagnosed with oro-facial-digital syndrome type 1. The second patient, a male with a heterozygous nonsense variant p.(Gln892Ter), presented with features resembling Simpson\u2013Golabi\u2013Behmel syndrome type 2, as previously reported under this diagnosis. The third patient, a male with another heterozygous nonsense variant p.(Glu879Ter), exhibited isolated primary ciliary dyskinesia without any syndromic features. Conclusions: This study contributes to the growing body of evidence on the expanding phenotypic spectrum of OFD1-associated disorders. It underscores the need for further investigation into the molecular mechanisms underlying the diverse presentations and the necessity of re-evaluating diagnostic classifications for conditions such as SGBS2 in the context of variants in the OFD1 gene.<\/jats:p>","DOI":"10.3390\/genes15121633","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T06:44:33Z","timestamp":1734677073000},"page":"1633","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Expanding the Genotypic and Phenotypic Spectrum of OFD1-Related Conditions: Three More Cases"],"prefix":"10.3390","volume":"15","author":[{"given":"Tatiana","family":"Kyian","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5871-8005","authenticated-orcid":false,"given":"Artem","family":"Borovikov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Anisimova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1285-9093","authenticated-orcid":false,"given":"Oksana","family":"Ryzhkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Bulakh","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Bragina","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"},{"name":"Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskiye Gory, 1, Build. 40, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Avakyan","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4460-7627","authenticated-orcid":false,"given":"Anna","family":"Demchenko","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Zabnenkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Kovalev","sequence":"additional","affiliation":[{"name":"Saint Petersburg State Budgetary Healthcare Institution \u201cChildren\u2019s City Hospital of St. Olga\u201d, 2 Zemledelcheskaya St., 194146 Saint-Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6612-6695","authenticated-orcid":false,"given":"Artem","family":"Bukhonin","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6395-0407","authenticated-orcid":false,"given":"Elena","family":"Kondratyeva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 1 Moskvorechye St., 115522 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1086\/318802","article-title":"Identification of the Gene for Oral-Facial-Digital Type I Syndrome","volume":"68","author":"Ferrante","year":"2001","journal-title":"Am. 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