{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:00:42Z","timestamp":1773673242762,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T00:00:00Z","timestamp":1611705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: CACNA1F-related disorders encompass progressive and non-progressive disorders, including \u00c5land island eye disease and incomplete congenital stationary night blindness. These two X-linked disorders are characterized by nystagmus, color vision defect, myopia, and electroretinography (ERG) abnormalities. Ocular hypopigmentation and iris transillumination are reported only in patients with \u00c5land island eye disease. Around 260 variants were reported to be associated with these two non-progressive disorders, with 19 specific to \u00c5land island eye disease and 14 associated with both \u00c5land island eye disease and incomplete congenital stationary night blindness. CACNA1F variants spread on the gene and further analysis are needed to reveal phenotype-genotype correlation. Case Report: A complete ocular exam and genetic testing were performed on a 13-year-old boy. A novel splice-site variant, c.4294-11C&gt;G in intron 36 in CACNA1F, was identified at hemizygous state in the patient and at heterozygous state in his asymptomatic mother and explained the phenotype synonymous with \u00c5land island eye disease and incomplete congenital stationary night blindness observed in the patient. Conclusion: We present a novel variant in the CACNA1F gene causing phenotypic and electrophysiologic findings indistinguishable from those of AIED\/CSNB2A disease. This finding further expands the mutational spectrum and our knowledge of CACNA1F-related disease.<\/jats:p>","DOI":"10.3390\/genes12020171","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T06:10:54Z","timestamp":1611727854000},"page":"171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Novel Splice-Site Variant in CACNA1F Causes a Phenotype Synonymous with \u00c5land Island Eye Disease and Incomplete Congenital Stationary Night Blindness"],"prefix":"10.3390","volume":"12","author":[{"given":"Usman","family":"Mahmood","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Hull Royal Infirmary, Hull 62807, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2532-4004","authenticated-orcid":false,"given":"C\u00e9cile","family":"M\u00e9j\u00e9case","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, London EC1V 9EL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed M. A.","family":"Ali","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital UAE, Abu Dhabi 62807, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1688-5360","authenticated-orcid":false,"given":"Mariya","family":"Moosajee","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology, London EC1V 9EL, UK"},{"name":"Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK"},{"name":"Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK"},{"name":"The Francis Crick Institute, London NW1 1AT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Igor","family":"Kozak","sequence":"additional","affiliation":[{"name":"Moorfields Eye Hospital UAE, Abu Dhabi 62807, United Arab Emirates"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,27]]},"reference":[{"key":"ref_1","first-page":"447","article-title":"A new eye syndrome with x\u2013chromosomal transmission. A family clan with fundus albinism, fovea hypoplasia, nystagmus, myopia, astigmatism and dyschromatopsia","volume":"144","author":"Forsius","year":"1964","journal-title":"Klin. Monatsbl. Augenheilkd"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1111\/j.1399-0004.1985.tb00421.x","article-title":"Aland eye disease: No albino misrouting","volume":"28","author":"Eriksson","year":"1985","journal-title":"Clin. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/bjo.79.5.424","article-title":"Aland island eye disease: Clinical and electrophysiological studies of a Welsh family","volume":"79","author":"Hawksworth","year":"1995","journal-title":"Br. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1111\/j.1755-3768.1991.tb02047.x","article-title":"Clinical and electroretinographic comparison between Aland island eye disease and a newly found related disease with X-chromosomal inheritance","volume":"69","author":"Carlson","year":"1991","journal-title":"Acta Ophthalmol. (Copenh)"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1136\/jmg.7.3.194","article-title":"Some notes on publications of Professor Arnold Sorsby and \u00c5land Eye Disease (Forsius-Eriksson syndrome)","volume":"7","author":"Waardenburg","year":"1970","journal-title":"J. Med. Genet."},{"key":"ref_6","unstructured":"Francois, J. (1968). ERG in a case of X-chromosomal pigment deficiency of fundus in combination with myopia, dyschromatopsia and defective dark adaptation. The Clinical Value of Electroretinography, Proceedings of the 5th ISCERG Symposium, Ghent, Belgium, Karger."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1111\/j.1755-3768.1973.tb06047.x","article-title":"Nystagmographical studies in Aland eye disease","volume":"51","author":"Waardenburg","year":"1973","journal-title":"Acta Ophthalmol. (Copenh)"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1167\/iovs.06-1103","article-title":"A novel CACNA1F gene mutation causes \u00c5land island eye disease","volume":"48","author":"Jalkanen","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/940","article-title":"An L-type calcium-channel gene mutated in incomplete X-linked congenital stationary night blindness","volume":"19","author":"Strom","year":"1998","journal-title":"Nat. Genet."},{"key":"ref_10","first-page":"3262","article-title":"A novel p.Gly603Arg mutation in CACNA1F causes \u00c5land island eye disease and incomplete congenital stationary night blindness phenotypes in a family","volume":"17","author":"Vincent","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/sj.ejhg.5200828","article-title":"Thirty distinct CACNA1F mutations in 33 families with incomplete type of XLCSNB and Cacna1f expression profiling I mouse retina","volume":"10","author":"Wutz","year":"2002","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_12","unstructured":"MacDonald, I.M., Hoang, S., and Tuupanen, S. (2019). X-linked congenital stationary night blindness. GeneReviews\u00ae [Internet], University of Washington. (Updated 3 July 2019)."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1006\/geno.2000.6204","article-title":"Isolation and characterization of a calcium channel gene, Cacnaf1, the murine orthologue of the gene for incomplete X-linked congenital stationary night blindness","volume":"66","author":"Naylor","year":"2000","journal-title":"Genomics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/366158a0","article-title":"Molecular determinants of Ca2+ selectivity and ion permeation in L-type Ca2+ channels","volume":"366","author":"Yang","year":"1993","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1002\/humu.23735","article-title":"Where are the missing gene defects in inherited retinal disorders? Intronic and synonymous variants contribute at least to 4% of CACNA1F-mediated inherited retinal disorders","volume":"40","author":"Zeitz","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3035","DOI":"10.1093\/hmg\/ddi336","article-title":"Mutation of the calcium channel gene Cacna1f disrupts calcium signaling, synaptic transmission and cellular organization in mouse retina","volume":"14","author":"Mansergh","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1001\/archopht.1986.01050190071042","article-title":"Congenital stationary night blindness with negative electroretinogram. A new classification","volume":"104","author":"Miyake","year":"1986","journal-title":"Arch. Ophthalmol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1001\/archopht.121.7.1028","article-title":"Retinal and optic disc atrophy associated with a CACNA1F mutation in a Japanese family","volume":"121","author":"Nakamura","year":"2003","journal-title":"Arch. Ophthalmol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1755-3768.1990.tb01923.x","article-title":"\u00c5land eye disease (Forsius-Eriksson-Miyake syndrome) with probability established in a Danish family","volume":"68","author":"Rosenberg","year":"1990","journal-title":"Acta Ophthalmol. (Copenh)"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.preteyeres.2014.09.001","article-title":"Congenital stationary night blindness: An analysis and update of genotype-phenotype correlations and pathogenic mechanisms","volume":"45","author":"Zeitz","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0008-4182(00)80031-9","article-title":"Clinical variability among patients with incomplete X-linked congenital stationary night blindness and a founder mutation in CACNA1F","volume":"35","author":"Boycott","year":"2000","journal-title":"Can. J. Ophthalmol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/2\/171\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:15:55Z","timestamp":1760159755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/2\/171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,27]]},"references-count":21,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["genes12020171"],"URL":"https:\/\/doi.org\/10.3390\/genes12020171","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,27]]}}}