{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T05:44:39Z","timestamp":1792820679288,"version":"4.5.0"},"reference-count":8,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"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":["Pediatr Nephrol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Autosomal recessive polycystic kidney disease is a cystic kidney disease with early onset and clinically characterized by enlarged echogenic kidneys, hypertension, varying degrees of kidney dysfunction, and liver fibrosis. It is most frequently caused by sequence variants in the <jats:italic>PKHD1<\/jats:italic> gene, encoding fibrocystin. In more rare cases, sequence variants in <jats:italic>DZIP1L<\/jats:italic> are seen, encoding the basal body protein DAZ interacting protein 1-like protein (DZIP1L). So far, only four different <jats:italic>DZIP1L<\/jats:italic> variants have been reported.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Four children from three consanguineous families presenting with polycystic kidney disease were selected for targeted or untargeted exome sequencing.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We identified two different, previously not reported homozygous <jats:italic>DZIP1L<\/jats:italic> sequence variants: c.193\u00a0T\u2009&gt;\u2009C; p.(Cys65Arg), and c.216C\u2009&gt;\u2009G; p.(Cys72Trp). Functional analyses of the c.216C\u2009&gt;\u2009G; p.(Cys72Trp) variant indicated mislocalization of mutant DZIP1L.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>In line with published data, our results suggest a critical role of the N-terminal domain for proper protein function. Although patients with <jats:italic>PKHD1<\/jats:italic>-associated autosomal recessive polycystic kidney disease often have liver abnormalities, none of the present four patients showed any clinically relevant liver involvement. Our data demonstrate the power and efficiency of next-generation sequencing-based approaches. While <jats:italic>DZIP1L-<\/jats:italic>related polycystic kidney disease certainly represents a rare form of the disease, our results emphasize the importance of including <jats:italic>DZIP1L<\/jats:italic> in multigene panels and in the data analysis of whole-exome sequencing for cystic kidney diseases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                <jats:p>A higher resolution version of the Graphical abstract is available as Supplementary information<\/jats:p>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00467-022-05441-4","type":"journal-article","created":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T19:02:42Z","timestamp":1645729362000},"page":"2657-2665","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Detection of DZIP1L mutations by whole-exome sequencing in consanguineous families with polycystic kidney disease"],"prefix":"10.1007","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0087-4739","authenticated-orcid":false,"given":"Jens Michael","family":"Hertz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Svenningsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Dimke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Buch","family":"Engelund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"N\u00f8rgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Marcussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helle Charlotte","family":"Thiesson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bergmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Larsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"5441_CR1","unstructured":"Sweeney WE, Avner ED (2019) Polycystic Kidney Disease, Autosomal Recessive. 2001 Jul 19 [Updated 2019 Feb 14]. In: Adam MP et al, editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132019. https:\/\/www.ncbi.nlm.nih.gov\/books\/. Assessed 31 January 2021"},{"key":"5441_CR2","doi-asserted-by":"publisher","first-page":"221","DOI":"10.3389\/fped.2017.00221","volume":"5","author":"C Bergmann","year":"2018","unstructured":"Bergmann C (2018) Genetics of Autosomal Recessive Polycystic Kidney Disease and Its Differential Diagnoses. Front Pediatr 5:221","journal-title":"Front Pediatr"},{"key":"5441_CR3","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1038\/ng.3871","volume":"49","author":"H Lu","year":"2017","unstructured":"Lu H, Galeano MCR, Ott E, Kaeslin G, Kausalya PJ, Kramer C, Ortiz-Br\u00fcchle N, Hilger N, Metzis V, Hiersche M, Tay SY, Tunningley R, Vij S, Courtney AD, Whittle B, W\u00fchl E, Vester U, Hartleben B, Neuber S, Frank V, Little MH, Epting D, Papathanasiou P, Perkins AC, Wright GD, Hunziker W, Gee HY, Otto EA, Zerres K, Hildebrandt F, Roy S, Wicking C, Bergmann C (2017) Mutations in DZIP1L, which encodes a ciliary-transition-zone protein, cause autosomal recessive polycystic kidney disease. Nat Genet 49:1025\u20131034","journal-title":"Nat Genet"},{"key":"5441_CR4","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1038\/s41436-021-01127-8","volume":"23","author":"E Schrezenmeier","year":"2021","unstructured":"Schrezenmeier E, Kremerskothen E, Halleck F, Staeck O, Liefeldt L, Choi M, Sch\u00fcler M, Weber U, Bachmann N, Grohmann M, Wagner T, Budde K, Bergmann C (2021) The underestimated burden of monogenic kidney disease in adults waitlisted for kidney transplantation. Genet Med 23:1219\u20131224","journal-title":"Genet Med"},{"key":"5441_CR5","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/978-1-59745-196-3_6","volume":"498","author":"HE Klock","year":"2009","unstructured":"Klock HE, Lesley SA (2009) The Polymerase Incomplete Primer Extension (PIPE) method applied to high-throughput cloning and site-directed mutagenesis. 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Am J Physiol Renal Physiol 13:F629\u2013F640","journal-title":"Am J Physiol Renal Physiol"},{"key":"5441_CR8","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.ajhg.2009.03.010","volume":"84","author":"HV Firth","year":"2009","unstructured":"Firth HV, Richards SM, Bevan AP, Clayton S, Corpas M, Rajan D, Van Vooren S, Moreau Y, Pettett RM, Carter NP (2009) DECIPHER: Database of chromosomal imbalance and phenotype in humans using Ensemble using resources. 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The Regional Committees on Health Research Ethics for Southern Denmark approved the use of kidney tissue for the functional analysis (S-20140159).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate and publication"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}