{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:13:28Z","timestamp":1782846808705,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The rapid spread of genome\u2010wide next\u2010generation sequencing in the molecular diagnosis of rare genetic disorders has produced increasing evidence of multilocus genomic variations in cases with a previously well\u2010characterized molecular diagnosis. Here, we describe two patients with a rare combination of skeletal abnormalities and retinal dystrophy caused by variants in the <jats:italic>SLC26A2<\/jats:italic> and <jats:italic>ABCA4<\/jats:italic> genes, respectively, in a family with parental consanguinity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Next\u2010generation sequencing and Sanger sequencing were performed to obtain a molecular diagnosis for the retinal and skeletal phenotypes, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic testing revealed that the sisters were homozygous for the p.(Cys653Ser) variant in <jats:italic>SLC26A2<\/jats:italic> and heterozygous for the missense p.(Pro68Leu) and splice donor c.6386+2C&gt;G variants in <jats:italic>ABCA4<\/jats:italic>. Segregation analysis confirmed the carrier status of the parents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Despite low frequency of occurrence, the detection of multilocus genomic variations in a single disease gene\u2010oriented approach can provide accurate diagnosis even in cases with high phenotypic complexity. A targeted sequencing approach can detect relationships between observed phenotypes and underlying genotypes, useful for clinical management.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1630","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T13:08:33Z","timestamp":1615900113000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Recessive multiple epiphyseal dysplasia and Stargardt disease in two sisters"],"prefix":"10.1002","volume":"9","author":[{"given":"Leonardo","family":"Gatticchi","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine Laboratory of Biochemistry University of Perugia Perugia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominika","family":"Ve\u0161el\u00e9nyiov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Natural Sciences University of Ss. Cyril and Methodius Trnava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Miertus","sequence":"additional","affiliation":[{"name":"G\u00e9nius n.o Trnava Slovakia"},{"name":"MAGI\u2019s Lab, Genetic Testing Laboratory Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1974-4937","authenticated-orcid":false,"given":"Paolo","family":"Enrico Maltese","sequence":"additional","affiliation":[{"name":"MAGI\u2019s Lab, Genetic Testing Laboratory Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1176-3359","authenticated-orcid":false,"given":"Elena","family":"Manara","sequence":"additional","affiliation":[{"name":"MAGI Euregio Bolzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisia","family":"Costantini","sequence":"additional","affiliation":[{"name":"MAGI\u2019s Lab, Genetic Testing Laboratory Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Benedetti","sequence":"additional","affiliation":[{"name":"MAGI\u2019s Lab, Genetic Testing Laboratory Rovereto Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darina","family":"\u010eurov\u010d\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Molecular Medicine Faculty of Medicine Slovak Healthcare University Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juraj","family":"Krajcovic","sequence":"additional","affiliation":[{"name":"Department of Biology Faculty of Natural Sciences University of Ss. 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