{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:09:43Z","timestamp":1790759383460,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Ciliopathies are a class of inherited severe human disorders that occur due to defective formation or function of cilia. The <jats:italic>RPGRIP1L<\/jats:italic> (retinitis pigmentosa GTPase regulator-interacting protein1-like) gene encodes for a ciliary protein involved in regulating cilia formation and function. Mutations in <jats:italic>RPGRIP1L<\/jats:italic> cause ciliopathies associated with severe embryonic defects, such as Meckel-Gruber Syndrome (MKS). Here we report <jats:italic>RPGRIP1L<\/jats:italic> mutation analysis in a family diagnosed with MKS. The clinical manifestations of the fetus included thoraco-lumbar open neural tube defect with associated Chiari type II malformation and hydrocephalus, bilateral club feet, and single right kidney\/ureter. Analysis of the parental DNA samples revealed that the father carried a previously reported mutation R1236C\/+ whereas the mother had a novel splice site mutation IVS6+1\u00a0G &amp;gt; A\/+ in <jats:italic>RPGRIP1L<\/jats:italic>. The splice site mutation resulted in the exclusion of in-frame exon 6 of <jats:italic>RPGRIP1L<\/jats:italic> (RPGRIP1L-\u2206Ex6) but expressed a stable protein in fibroblasts derived from the parents\u2019 skin biopsies. The GFP-RPGRIP1L-\u2206Ex6 mutant protein exhibited relatively reduced ciliary localization in transiently-transfected cultured RPE-1 cells. Taken together, this study identifies a novel RPGRIP1L variant RPGRIP1L-\u2206Ex6, which in combination with RPGRIP1L-R1236C is associated with MKS. We also suggest that the deletion of exon 6 of RPGRIP1L leads to reduced ciliary localization of RPGRIP1L, indicating a plausible mechanism of associated disease.<\/jats:p>","DOI":"10.3389\/fgene.2022.982127","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T05:45:49Z","timestamp":1660887949000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Prenatal phenotype analysis and mutation identification of a fetus with meckel gruber syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Laura","family":"Moreno-Leon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco A.","family":"Quezada-Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Bilsbury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Kiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Guerin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemant","family":"Khanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"105236","DOI":"10.1016\/j.nbd.2020.105236","article-title":"Cilia, ciliopathies and hedgehog-related forebrain developmental disorders","volume":"150","author":"Andreu-Cervera","year":"2021","journal-title":"Neurobiol. 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