{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:23Z","timestamp":1792790363463,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,30]]},"group-title":"Genetic and Genomic Medicine","reference-count":18,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["NIDDK P30 DK056338"],"award-info":[{"award-number":["NIDDK P30 DK056338"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research, Development and Innovation Office of Hungary","award":["NKFIH 138669"],"award-info":[{"award-number":["NKFIH 138669"]}],"id":[{"id":"https:\/\/ror.org\/03g2am276","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Short-rib polydactyly syndrome type IV (Beemer-Langer syndrome) is a lethal skeletal ciliopathy that can result from biallelic pathogenic variants in\n                    <jats:italic>KIAA0586<\/jats:italic>\n                    (TALPID3). Earlier clinical observations suggested an unusually high occurrence of this phenotype in Romani families from the Carpathian Basin. Methods: Whole-exome sequencing was performed in affected individuals from five independent families, and the frequency of\n                    <jats:italic>KIAA0586<\/jats:italic>\n                    c.1815G&gt;A was assessed in a Hungarian Romani genetic database of 500 individuals. Results: The affected individuals were homozygous for c.1815G&gt;A, a splice-disrupting variant previously shown to cause exon 14 skipping. Four families self-identified as Roma from Hungary and one affected individual was from Turkey. Six heterozygous carriers were identified among 500 individuals in the Hungarian Romani cohort, corresponding to an allele frequency of 0.6%. This was markedly higher than the frequencies cited from ALFA (0.01%) and gnomAD (0.0014%). The Hungarian-Romani and Turkish affected individuals also shared genotypes at informative markers flanking the variant, supporting a shared ancestral haplotype. Conclusions: These observations strengthen evidence that\n                    <jats:italic>KIAA0586<\/jats:italic>\n                    c.1815G&gt;A is a founder allele enriched in at least some Romani populations. The data support consideration of ancestry-informed carrier testing in appropriately counseled families. Historical admixture may explain the occurrence of the same haplotype in a Turkish case, but this remains a hypothesis requiring broader population-genomic confirmation.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.29.26363928","type":"posted-content","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:20:13Z","timestamp":1790796013000},"source":"Crossref","is-referenced-by-count":0,"title":["A\n                  <i>KIAA0586<\/i>\n                  c.1815G&gt;A Founder Allele Associated with Short-Rib Polydactyly Syndrome Type IV in Romani Families"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4146-1335","authenticated-orcid":false,"given":"Richard","family":"Kellermayer","sequence":"first","affiliation":[{"name":"Division of Pediatric Gastroenterology, Texas Children\u2019s Hospital, Baylor College of Medicine, Houston, TX, USA"},{"name":"USDA\/ARS Children\u2019s Nutrition Research Center, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Farooq","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics & Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Bene","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of P\u00e9cs, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nursel H.","family":"Elcioglu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics, Marmara University School of Medicine, Istanbul, Turkey"},{"name":"Eastern Mediterranean University Medical School, Famagusta, Mersin 10, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Alan","family":"Harris","sequence":"additional","affiliation":[{"name":"Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA"},{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reka G.","family":"Szigeti","sequence":"additional","affiliation":[{"name":"Department of Pathology & Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Teszas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of P\u00e9cs, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Tommerup","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars A.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela","family":"Melegh","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of P\u00e9cs, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinga","family":"Hadzsiev","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, University of P\u00e9cs, P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100607552196000_2026.09.29.26363928v1.1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.063602"},{"key":"2026100607552196000_2026.09.29.26363928v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.06.003"},{"key":"2026100607552196000_2026.09.29.26363928v1.3","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.06602"},{"key":"2026100607552196000_2026.09.29.26363928v1.4","doi-asserted-by":"publisher","DOI":"10.1136\/jmg-2022-108725"},{"key":"2026100607552196000_2026.09.29.26363928v1.5","first-page":"2816","article-title":"High incidence of short rib-polydactyly syndrome type IV in a Hungarian Roma subpopulation","volume":"140","year":"2006","journal-title":"Am J Med Genet A"},{"key":"2026100607552196000_2026.09.29.26363928v1.6","doi-asserted-by":"crossref","first-page":"e19169","DOI":"10.1097\/MD.0000000000019169","article-title":"The splice c.1815G>A variant in KIAA0586 results in a phenotype bridging short-rib-polydactyly and oral-facial-digital syndrome: a case report and literature review","volume":"99","year":"2020","journal-title":"Medicine (Baltimore)"},{"key":"2026100607552196000_2026.09.29.26363928v1.7","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msaa156"},{"key":"2026100607552196000_2026.09.29.26363928v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008417"},{"key":"2026100607552196000_2026.09.29.26363928v1.9","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/ejhg.2015.201","article-title":"Origins, admixture and founder lineages in European Roma","volume":"24","year":"2016","journal-title":"Eur J Hum Genet"},{"key":"2026100607552196000_2026.09.29.26363928v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.10.039"},{"key":"2026100607552196000_2026.09.29.26363928v1.11","doi-asserted-by":"crossref","first-page":"e58633","DOI":"10.1371\/journal.pone.0058633","article-title":"Reconstructing Roma history from genome-wide data","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"2026100607552196000_2026.09.29.26363928v1.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-023-02579-5"},{"key":"2026100607552196000_2026.09.29.26363928v1.13","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.3390\/genes13112068","article-title":"Population genetics of the European Roma\u2014a review","volume":"13","year":"2022","journal-title":"Genes (Basel)"},{"key":"2026100607552196000_2026.09.29.26363928v1.14","doi-asserted-by":"crossref","first-page":"558","DOI":"10.3389\/fgene.2019.00558","article-title":"Revealing the genetic impact of the Ottoman occupation on ethnic groups of East-Central Europe and on the Roma population of the area","volume":"10","year":"2019","journal-title":"Front Genet"},{"key":"2026100607552196000_2026.09.29.26363928v1.15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1996.tb02373.x"},{"key":"2026100607552196000_2026.09.29.26363928v1.16","doi-asserted-by":"publisher","DOI":"10.1002\/jcu.20603"},{"key":"2026100607552196000_2026.09.29.26363928v1.17","unstructured":"Wallace SE . 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