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Recently, 14 causative genes of LCA were reported. We performed whole-exome sequencing (WES) for Japanese siblings, and identified a novel homozygous nonsense mutation in the RPGR-interacting protein 1 (<jats:italic>RPGRIP1<\/jats:italic>) gene. We also report their follow-up data over 27\u2009years.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>Patient 1 is a 37-year-old male. In 1992, his eye position indicated orthophoria, however, horizontal nystagmus was evident, and he complained of photophobia. His best corrected decimal visual acuity (BCVA) was 0.2 (S\u2009+\u20096.5\/C-3.5\/170\u00b0) OD and 0.1 (S\u2009+\u20096.0\/C-2.5\/10\u00b0) OS. Fundus examination revealed bisymmetrical inferior focal retinal pigment epithelium (RPE) mottling. Bright-flash electroretinogram (ERG) revealed a subnormal pattern, while 30\u2009Hz flicker ERG was non-recordable in both eyes. At his final visit in 2019, his BCVA was 0.09 (S\u2009+\u20093.5\/C-3.5\/180\u00b0) OD and 0.09 (S\u2009+\u20093.0\/C-4.0\/10\u00b0) OS. Patient 2, a 34-year-old female, is the sibling of patient 1. In 1992, her BCVA was 0.05 (S\u2009+\u20096.0) OD and 0.06 (S\u2009+\u20095.0) OS. She was in a chin-up position during visual acuity testing. Horizontal nystagmus was evident, and she also complained of photophobia. Bright-flash ERG was severely attenuated, and 30\u2009Hz flicker ERG was non-recordable in both eyes. At her final visit in 2019, her BCVA was 0.02 (uncorrectable) OD and 0.03 (uncorrectable) OS. There were no other patients with LCA in their family and their parents were non-consanguineous. WES revealed a homozygous, consecutive, two-nucleotide variation in the <jats:italic>RPGRIP1<\/jats:italic> gene (NM_020366: exon15:c.G2294A and c.C2295A, p.C765X), resulting in a premature stop codon. We interpreted this variation as a novel pathogenic mutation of <jats:italic>RPGRIP1<\/jats:italic> that contributes to LCA6 development.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Herein, we report a novel nonsense mutation of <jats:italic>RPGRIP1<\/jats:italic> in two patients with LCA6 and present their long-term follow-up data. These clinical data linked to genotypes provide important information for the development of new treatments, such as gene therapy, as well as for genetic counseling.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12886-020-01577-9","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T10:03:45Z","timestamp":1596189825000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Novel mutation identified in Leber congenital amaurosis - a case report"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-5701","authenticated-orcid":false,"given":"Shigeru","family":"Sato","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Morimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sayaka","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kikuko","family":"Hotta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Fujikado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motokazu","family":"Tsujikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohji","family":"Nishida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"1577_CR1","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1093\/hmg\/11.10.1169","volume":"11","author":"FPM Cremers","year":"2002","unstructured":"Cremers FPM, van den Hurk JAJM, den Hollander AI. 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