{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:05:30Z","timestamp":1780599930113,"version":"3.54.1"},"reference-count":32,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Czech Ministry of Health","award":["00064203"],"award-info":[{"award-number":["00064203"]}]},{"name":"Czech Medical Council","award":["NW24-06-00083"],"award-info":[{"award-number":["NW24-06-00083"]}]},{"name":"Czech Ministry of Youth Education and Sports","award":["LM2018132"],"award-info":[{"award-number":["LM2018132"]}]},{"name":"University of Debrecen Scientific Research Bridging Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Smith\u2013Lemli\u2013Opitz syndrome (SLOS) is an inborn error of cholesterol biosynthesis, caused by biallelic mutations in the DHCR7 gene. Genotype\u2013phenotype correlations regarding DHCR7 variants could explain the variation in severity, ranging from in utero demise or severe SLOS to a mild phenotype. Clinical recognition can be challenging. This study aimed to determine the frequency of SLOS carriers in the Central European population, as well as the mutational spectrum of DHCR7 in these carriers. Methods: A retrospective analysis of DHCR7 variants was conducted using next-generation sequencing data from 55,289 individuals in Czech and Hungarian genetic laboratories. Results: The SLOS carrier frequency and the mutational spectrum of the DHCR7 gene in its carriers were established in the Czech and Hungarian sub-cohorts. In the combined dataset, we identified causative DHCR7 variants on 1567 alleles among 55,289 tested individuals, contributing to an SLOS carrier frequency of 2.83%. Of the 31 DHCR7 variants detected, the c.452G&gt;A variant was the most prevalent, accounting for 1.8% of all detected alleles in our cohorts. In contrast, the c.964-1G&gt;C variant was more frequent in non-Finnish Europeans, as indicated by the gnomAD 4.1.0 database. The DHCR7 mutational spectra of patients and carriers were comparable in terms of the most common variants. Conclusions: The high SLOS carrier frequency (2.83%) underscores the importance of SLOS carrier screening in Central European populations. The prevalent DHCR7 null mutations and their potential combinations may explain the lower-than-expected prevalence of SLOS, whilst Central and Eastern European populations remain likely underrepresented in the current gnomAD database.<\/jats:p>","DOI":"10.3390\/genes17020164","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T14:35:46Z","timestamp":1769783746000},"page":"164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence of Smith\u2013Lemli\u2013Opitz Syndrome Carriers and the Spectrum of DHCR7 Pathogenic Variants in Representative Czech and Hungarian Population Cohorts"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6082-3591","authenticated-orcid":false,"given":"Eszter","family":"Kov\u00e1cs","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2836-3383","authenticated-orcid":false,"given":"Zsuzsanna","family":"Sz\u0171cs","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav","family":"Hor\u0148\u00e1k","sequence":"additional","affiliation":[{"name":"Repromeda, Assisted Reproduction Centre, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kub\u00ed\u010dek","sequence":"additional","affiliation":[{"name":"Repromeda, Assisted Reproduction Centre, 625 00 Brno, Czech Republic"},{"name":"Department of Histology and Embryology, Faculty of Medicine, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina","family":"Weisov\u00e1","sequence":"additional","affiliation":[{"name":"Repromeda, Assisted Reproduction Centre, 625 00 Brno, Czech Republic"},{"name":"Department of Experimental Biology, Faculty of Science, Masaryk University, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina","family":"Vesel\u00e1","sequence":"additional","affiliation":[{"name":"Repromeda, Assisted Reproduction Centre, 625 00 Brno, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Kr\u016fzov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Applied Biotechnologies a.s., 199 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Geryk","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and Motol and Homolka University Hospital, 150 06 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0627-9124","authenticated-orcid":false,"given":"Jan","family":"Dibl\u00edk","sequence":"additional","affiliation":[{"name":"GENNET, Centre of Medical Genetics and Reproductive Medicine, 170 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Bitt\u00f3ov\u00e1","sequence":"additional","affiliation":[{"name":"GENNET, Centre of Medical Genetics and Reproductive Medicine, 170 00 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5173-5280","authenticated-orcid":false,"suffix":"Jr.","given":"Milan","family":"Macek","sequence":"additional","affiliation":[{"name":"Department of Biology and Medical Genetics, Second Faculty of Medicine, Charles University and Motol and Homolka University Hospital, 150 06 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3397-2829","authenticated-orcid":false,"given":"Istv\u00e1n","family":"Balogh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Koczok","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"},{"name":"Doctoral School of Molecular Cell and Immune Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1136\/jmg.37.5.321","article-title":"The Smith\u2013Lemli\u2013Opitz Syndrome","volume":"37","author":"Kelley","year":"2000","journal-title":"J. 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