{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:51:07Z","timestamp":1777438267595,"version":"3.51.4"},"reference-count":37,"publisher":"BMJ","issue":"9","funder":[{"name":"Foundation Fighting Blindness"},{"name":"the Netherlands Organization for Scientific Research"},{"DOI":"10.13039\/501100010372","name":"Rotterdamse Stichting Blindenbelangen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010372","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010374","name":"Stichting Blindenhulp","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010374","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010331","name":"Stichting voor Ooglijders","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010331","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100010377","name":"Stichting tot Verbetering van het Lot der Blinden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010377","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the European Community's Seventh Framework Programmes FP7\/2009"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2017,2,27]]},"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recent findings suggesting that <jats:italic>Abelson helper integration site 1<\/jats:italic> (<jats:italic>AHI1<\/jats:italic>) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether <jats:italic>AHI1<\/jats:italic> variants cause non-syndromic retinitis pigmentosa (RP).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in <jats:italic>AHI1<\/jats:italic> were predicted by three-dimensional structure homology modelling. Ciliary parameters were evaluated in patient\u2019s fibroblasts, and recombinant mutant proteins were expressed in ciliated retinal pigmented epithelium cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the three patients with RP, three sets of compound heterozygous variants were detected in <jats:italic>AHI1<\/jats:italic> (c.2174G&gt;A; p.Trp725* and c.2258A&gt;T; p.Asp753Val, c.660delC; p.Ser221Glnfs*10 and c.2090C&gt;T; p.Pro697Leu, c.2087A&gt;G; p.His696Arg and c.2429C&gt;T; p.Pro810Leu). All four missense variants were present in the conserved WD40 domain of Jouberin, the ciliary protein encoded by <jats:italic>AHI1<\/jats:italic>, with variable predicted implications for the domain structure. No significant changes in the percentage of ciliated cells, nor in cilium length or intraflagellar transport were detected. However, expression of mutant recombinant Jouberin in ciliated cells showed a significantly decreased enrichment at the ciliary base.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This report confirms that mutations in <jats:italic>AHI1<\/jats:italic> can underlie autosomal recessive RP. Moreover, it structurally and functionally validates the effect of the RP-associated <jats:italic>AHI1<\/jats:italic> variants on protein function, thus proposing a new genotype\u2013phenotype correlation for <jats:italic>AHI1<\/jats:italic> mutation associated retinal ciliopathies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2016-104200","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T20:50:15Z","timestamp":1493153415000},"page":"624-632","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Missense mutations in the WD40 domain of <i>AHI1<\/i> cause non-syndromic retinitis pigmentosa"],"prefix":"10.1136","volume":"54","author":[{"given":"Thanh-Minh T","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Hull","sequence":"additional","affiliation":[{"name":"UniversityCollege London, Instituteof Ophthalmology, London, United Kingdom"},{"name":"Moorfields Eye Hospital, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald","family":"Roepman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L Ingeborgh","family":"van den Born","sequence":"additional","affiliation":[{"name":"The Rotterdam Eye Hospital, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Machteld M","family":"Oud","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"de Vrieze","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisette","family":"Hetterschijt","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stef J F","family":"Letteboer","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia E C","family":"van Beersum","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen A","family":"Blokland","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helger G","family":"Yntema","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frans P M","family":"Cremers","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul A","family":"van der Zwaag","sequence":"additional","affiliation":[{"name":"Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The 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