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In such cases, long-range information is required to resolve the rearrangement, identify disrupted genes and, in symptomatic carriers, pinpoint the disease-causing mechanisms. Here, we report an individual with autism, epilepsy and osteoporosis and a de novo balanced reciprocal translocation: t(17;19) (p13;p11). The genomic DNA was analyzed by short-, linked- and long-read genome sequencing, as well as optical mapping. Transcriptional consequences were assessed by transcriptome sequencing of patient-specific neuroepithelial stem cells derived from induced pluripotent stem cells (iPSC). The translocation breakpoints were only detected by long-read sequencing, the first on 17p13, located between exon 1 and exon 2 of MINK1 (Misshapen-like kinase 1), and the second in the chromosome 19 centromere. Functional validation in induced neural cells showed that MINK1 expression was reduced by &gt;50% in the patient\u2019s cells compared to healthy control cells. Furthermore, pathway analysis revealed an enrichment of changed neural pathways in the patient\u2019s cells. Altogether, our multi-omics experiments highlight MINK1 as a candidate monogenic disease gene and show the advantages of long-read genome sequencing in capturing centromeric translocations.<\/jats:p>","DOI":"10.3390\/ijms23169392","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T22:23:13Z","timestamp":1661120593000},"page":"9392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Multi-Omic Investigations of a 17\u201319 Translocation Links MINK1 Disruption to Autism, Epilepsy and Osteoporosis"],"prefix":"10.3390","volume":"23","author":[{"given":"Jesper","family":"Eisfeldt","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden"},{"name":"Department of Clinical Genetics, Karolinska University Hospital, 171 76 Stockholm, Sweden"},{"name":"Science for Life Laboratory, Karolinska Institutet Science Park, 171 65 Solna, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Schuy","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva-Lena","family":"Stattin","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 08 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Kvarnung","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden"},{"name":"Department of Clinical Genetics, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1634-8610","authenticated-orcid":false,"given":"Anna","family":"Falk","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicum, Karolinska Institutet, 171 77 Stockholm, Sweden"},{"name":"Lund Stem Cell Center, Department of Experimental Medical Science, Lund University, 221 84 Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Feuk","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Uppsala University, 751 08 Uppsala, Sweden"},{"name":"Science for Life Laboratory, Uppsala University, 752 37 Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0806-5602","authenticated-orcid":false,"given":"Anna","family":"Lindstrand","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden"},{"name":"Department of Clinical Genetics, Karolinska University Hospital, 171 76 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/ng.329","article-title":"Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence","volume":"41","author":"Benko","year":"2009","journal-title":"Nat. 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