{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:18:38Z","timestamp":1771395518849,"version":"3.50.1"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>\n                    Steel syndrome (STLS, OMIM# 615155) is a rare skeletal dysplasia associated with biallelic pathogenic variants in\n                    <jats:italic>COL27A1<\/jats:italic>\n                    gene. To date, more than 60 patients with STLS have been reported in the literature, the majority of whom are Puerto Rican. STLS in all individuals from this population is associated with the homozygous p.Gly697Arg missense variant, confirming the founder effect. Meanwhile, just 17 cases from 14 unrelated non-Puerto Rican families have been reported, including two fetuses. Here we present two pediatric cases of STLS from Russian and Uzbek populations, associated with two novel compound heterozygous splice variants c.2673 + 4A &amp;gt; G, c.2619 + 1G &amp;gt; A and a novel homozygous missense variant c.3988G &amp;gt; C p. (Gly1330Arg). Splicing assay was performed to investigate the novel donor splice site variants' effects on mRNA structure and expression. Both cases demonstrated skeletal features characteristic of STLS, including acetabular dysplasia or hip dislocation, carpal coalition, radial head dislocation, with additional extraskeletal manifestations observed in one patient. A review of 63 STLS cases revealed key diagnostic criteria present in the majority of individuals, though phenotypic variability was observed depending on variant type and population origin. It is proposed that biallelic Gly substitutions within the triple-helical domain associated with the \u2018classic' skeletal phenotype of STLS initially characterized in Steel's study. In contrast, patients with homozygous or compound heterozygous frameshift or nonsense variants more frequently demonstrate a higher prevalence of extraskeletal manifestations and severe short stature. Our study expands the genetic and clinical spectrum of STLS in non-Puerto Rican populations and explores potential genotype-phenotype correlations, which will contribute to early disease diagnosis and the selection of optimal patient management strategies, avoiding unnecessary interventions.\n                  <\/jats:p>","DOI":"10.3389\/fmed.2026.1730466","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:34:03Z","timestamp":1771392843000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the clinical and genetic spectrum of Steel syndrome: two case reports and review of the literature"],"prefix":"10.3389","volume":"13","author":[{"given":"Daria","family":"Gorodilova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Kenis","sequence":"additional","affiliation":[{"name":"H.Turner National Medical Research Center for Children's Orthopedics and Trauma Surgery","place":["Saint-Petersburg, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khushnud","family":"Rustamov","sequence":"additional","affiliation":[{"name":"Republican Specialized Scientific and Practical Center for Traumatology and Orthopedics","place":["Tashkent, Uzbekistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria","family":"Akimova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Merkuryeva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Morgul","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alyona","family":"Grigorieva","sequence":"additional","affiliation":[{"name":"Department of Traumatology and Orthopedics, Saratov State Medical University named after V.I. Razumovsky","place":["Saratov, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliia","family":"Andreeva","sequence":"additional","affiliation":[{"name":"Saratov Regional Children's Clinical Hospital","place":["Saratov, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Zabnenkova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Bulakh","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis","family":"Chistol","sequence":"additional","affiliation":[{"name":"Tashkent Research Center for Medical Genetics","place":["Tashkent, Uzbekistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasibakhon","family":"Raimkhodjaeva","sequence":"additional","affiliation":[{"name":"Tashkent Research Center for Medical Genetics","place":["Tashkent, Uzbekistan"]},{"name":"Immunogen Test LLC at Institute of Immunology and Human Genomics of the Academy of Science of the Republic of Uzbekistan","place":["Tashkent, Uzbekistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Lavrov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]},{"name":"Tashkent Research Center for Medical Genetics","place":["Tashkent, Uzbekistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatyana","family":"Hegay","sequence":"additional","affiliation":[{"name":"Immunogen Test LLC at Institute of Immunology and Human Genomics of the Academy of Science of the Republic of Uzbekistan","place":["Tashkent, Uzbekistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamara","family":"Aripova","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Human Genomics of the Academy of Science of the Republic of Uzbekistan","place":["Tashkent, Uzbekistan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergey","family":"Kutsev","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Markova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics","place":["Moscow, Russia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199302000-00013","article-title":"A syndrome of dislocated hips and radial heads, carpal coalition, and short stature in Puerto Rican children","author":"Steel","year":"1993","journal-title":"J Bone Joint Surg Am."},{"key":"B2","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1097\/BPO.0b013e3181d3e464","article-title":"Steel syndrome: Dislocated hips and radial heads, carpal coalition, scoliosis, short stature, and characteristic facial features","volume":"30","author":"Flynn","year":"2010","journal-title":"J Pediatr Orthop."},{"key":"B3","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1038\/ejhg.2014.107","article-title":"Mutations in COL27A1 cause Steel syndrome and suggest a founder mutation effect in the Puerto Rican population","volume":"23","author":"Gonzaga-Jauregui","year":"2015","journal-title":"Eur J Hum Genet."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2022.104521","article-title":"Steel syndrome: report of three patients, including monozygotic twins and review of clinical and mutation profiles","author":"Girisha","year":"2022","journal-title":"Eur J Med Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00428-020-02979-2","article-title":"Histopathology of recurrent Steel syndrome in fetuses caused by novel variants of COL27A1 gene","volume":"479","author":"Frigola","year":"2021","journal-title":"Virchows Arch."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-020-0632-x","article-title":"Functional biology of the Steel syndrome founder allele and evidence for clan genomics derivation of COL27A1 pathogenic alleles worldwide","author":"Gonzaga-Jauregui","year":"2020","journal-title":"Eur J. 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