{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:56:28Z","timestamp":1790632588138,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Meier\u2013Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, the absence of or hypoplastic patellae and other skeletal anomalies. Skeletal symptoms overlapping with other syndromes make MGS difficult to diagnose clinically. We describe a 3-year-old boy with short stature, recurrent respiratory infections, short-rib dysplasia, tower head and facial dysmorphisms who was admitted to the Tomsk Genetic Clinic to verify a clinical diagnosis of Jeune syndrome. Clinical exome sequencing revealed two variants (compound heterozygosity) in the ORC6 gene: c.2T&gt;C(p.Met1Thr) and c.449+5G&gt;A. In silico analysis showed the pathogenicity of these two mutations and predicted a decrease in donor splicing site strength for c.449+5G&gt;A. An in vitro minigene assay indicated that variant c.449+5G&gt;A causes complete skipping of exon 4 in the ORC6 gene. The parents requested urgent prenatal testing for MGS for the next pregnancy, but it ended in a miscarriage. Our results may help prevent MGS misdiagnosis in the future. We also performed in silico and functional analyses of ORC6 mutations and developed a restriction fragment length polymorphism and haplotype-based short-tandem-repeat assay for prenatal genetic testing for MGS. These findings should elucidate MGS etiology and improve the quality of genetic counselling for affected families.<\/jats:p>","DOI":"10.3390\/ijms23169234","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T21:23:56Z","timestamp":1660771436000},"page":"9234","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Meier\u2013Gorlin Syndrome: Clinical Misdiagnosis, Genetic Testing and Functional Analysis of ORC6 Mutations and the Development of a Prenatal Test"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0673-4094","authenticated-orcid":false,"given":"Maria S.","family":"Nazarenko","sequence":"first","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, Russia"},{"name":"Department of Medical Genetics, Siberian State Medical University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8827-4756","authenticated-orcid":false,"given":"Iuliia V.","family":"Viakhireva","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7293-3438","authenticated-orcid":false,"given":"Mikhail Y.","family":"Skoblov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena V.","family":"Soloveva","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3226-1750","authenticated-orcid":false,"given":"Aleksei A.","family":"Sleptcov","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludmila P.","family":"Nazarenko","sequence":"additional","affiliation":[{"name":"Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, 634050 Tomsk, Russia"},{"name":"Department of Medical Genetics, Siberian State Medical University, 634050 Tomsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s13023-015-0322-x","article-title":"Meier-Gorlin syndrome","volume":"10","author":"Hoefsloot","year":"2015","journal-title":"Orphanet J. 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