{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:44:35Z","timestamp":1790603075288,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["K2012-64X-14506-10-5"],"award-info":[{"award-number":["K2012-64X-14506-10-5"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003792","name":"Hj\u00e4rnfonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003792","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006741","name":"Stiftelsen Frimurare Barnhuset i Stockholm","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006741","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004047","name":"Karolinska Institutet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003514","name":"Kommunfullm\u00e4ktige, Stockholms Stad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003514","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004063","name":"Knut och Alice Wallenbergs Stiftelse","doi-asserted-by":"publisher","award":["KAW 2011.0218"],"award-info":[{"award-number":["KAW 2011.0218"]}],"id":[{"id":"10.13039\/501100004063","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The bladder exstrophy\u2010epispadias complex (BEEC) is a congenital malformation of the bladder and urethra. The underlying causes of this malformation are still largely unknown; however, aside from environment, genetics is thought to play an essential role. The recurrent 22q11.2 microduplication is the most persistently detected genetic aberration found in BEEC cases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed array comparative genomic hybridization (array\u2010CGH) analysis of 76 Swedish BEEC patients. Statistical analysis was performed on current dataset pooled with previously published data on the 22q11.2 microduplication in BEEC patients. We performed massive parallel sequencing (MPS) of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication followed by functional studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified three additional cases with the 22q11.2 microduplication. Pooling data from this study with previously published reports showed a statistically significant enrichment of the 22q11.2 microduplication in BEEC patients (2.61% in cases vs. 0.08% in controls; OR\u00a0=\u00a032.6;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a08.7\u00a0\u00d7\u00a010\n                      <jats:sup>\u22124<\/jats:sup>\n                      ). MPS of the 22q11.2 region in 20 BEEC patients without the 22q11.2 microduplication identified a novel variant in\n                      <jats:italic>LZTR1<\/jats:italic>\n                      (p.Ser698Phe) in one patient. Functional evaluation of the\n                      <jats:italic>LZTR1<\/jats:italic>\n                      p.Ser698Phe variant in live NIH 3T3 cells showed that the concentration and cytoplasmic mobility differ between the Lztr1\n                      <jats:sub>wt<\/jats:sub>\n                      and Lztr1\n                      <jats:sub>mut<\/jats:sub>\n                      , indicating a potential functional effect of the LZTR1\n                      <jats:sub>mut<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study further emphasizes the involvement of the 22q11.2 region in BEEC development and highlights\n                      <jats:italic>LZTR1<\/jats:italic>\n                      as a candidate gene underlying the urogenital malformation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.666","type":"journal-article","created":{"date-parts":[[2019,5,2]],"date-time":"2019-05-02T01:16:02Z","timestamp":1556759762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Further support linking the 22q11.2 microduplication to an increased risk of bladder exstrophy and highlighting\n                    <i>LZTR1<\/i>\n                    as a candidate gene"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1042-618X","authenticated-orcid":false,"given":"Johanna","family":"Lundin","sequence":"first","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health Karolinska Institutet Stockholm Sweden"},{"name":"Department of Clinical Genetics Karolinska University Hospital Stockholm 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