{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T01:10:22Z","timestamp":1780535422334,"version":"3.54.1"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T00:00:00Z","timestamp":1705881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the <jats:italic>AVPR2<\/jats:italic> gene. Single nucleotide variants and small insertions\/deletions in <jats:italic>AVPR2<\/jats:italic> are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving <jats:italic>AVPR2<\/jats:italic> are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of <jats:italic>AVPR2<\/jats:italic> in a Czech family identified for the first time by targeted long-read sequencing (T-LRS).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A male proband with X-linked NDI underwent clinical sequencing of the <jats:italic>AVPR2<\/jats:italic> gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>By T-LRS, a novel 7.5\u2009kb deletion of <jats:italic>AVPR2<\/jats:italic> causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands\u00b4 mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Identifying the 7.5\u2009kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-024-01801-1","type":"journal-article","created":{"date-parts":[[2024,1,22]],"date-time":"2024-01-22T14:02:36Z","timestamp":1705932156000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeted long-read sequencing identified a causal structural variant in X-linked nephrogenic diabetes insipidus"],"prefix":"10.1186","volume":"17","author":[{"given":"Luk\u00e1\u0161","family":"Strych","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"\u010cern\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00e9ta","family":"Hejnalov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Zavoral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavla","family":"Komrskov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jitka","family":"Tejcov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Bitar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Sl\u00e1dkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"S\u00fdkora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"\u0160ubrt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,22]]},"reference":[{"key":"1801_CR1","volume-title":"Hereditary nephrogenic diabetes insipidus","author":"N Knoers","year":"1993","unstructured":"Knoers N, Lemmink H. 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Written informed consent was obtained from all subjects and\/or their legal guardian(s). All methods were carried out in accordance with relevant guidelines and regulations.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the parents of the child for the publication of clinical details.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29"}}