{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:00:56Z","timestamp":1777510856041,"version":"3.51.4"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T00:00:00Z","timestamp":1645142400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["418081722"],"award-info":[{"award-number":["418081722"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["433158657"],"award-info":[{"award-number":["433158657"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Variants in MFSD8 can cause neuronal ceroid lipofuscinoses (NCLs) as well as nonsyndromic retinopathy. The mutation spectrum includes mainly missense and stop variants, but splice sites and frameshift variants have also been reported. To date, apparently synonymous substitutions have not been shown to cause MFSD8-associated diseases. We report two closely related subjects from a consanguineous Turkish family who presented classical features of NCLs but demonstrated marked intrafamilial variability in age at the onset and severity of symptoms. In fact, the difference in the onset of first neurologic symptoms was 15 years and that of ophthalmologic symptoms was 12 years. One subject presented an intellectual disability and a considerable cerebellar ataxia syndrome, while the other subject showed no intellectual disability and only a mild atactic syndrome. The diagnostic genetic testing of both subjects based on genome sequencing prioritized a novel, apparently synonymous variant in MFSD8, which was found in homozygosity in both subjects. The variant was not located within an integral part of the splice site consensus sequences. However, the bioinformatic analyses suggested that the mutant allele is more likely to cause exon skipping due to an altered ratio of exonic splice enhancer and silencer motifs. Exon skipping was confirmed in vitro by minigene assays and in vivo by RNA analysis from patient lymphocytes. The mutant transcript is predicted to result in a frameshift and, if translated, in a truncated protein. Synonymous variants are often given a low priority in genetic diagnostics because of their expected lack of functional impact. This study highlights the importance of investigating the impact of synonymous variants on splicing.<\/jats:p>","DOI":"10.3390\/ijms23042271","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T08:18:05Z","timestamp":1645431485000},"page":"2271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A Novel, Apparently Silent Variant in MFSD8 Causes Neuronal Ceroid Lipofuscinosis with Marked Intrafamilial Variability"],"prefix":"10.3390","volume":"23","author":[{"given":"Milda","family":"Reith","sequence":"first","affiliation":[{"name":"Centre for Ophthalmology, University Eye Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lena","family":"Zeltner","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research and Center for Neurology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Centre for Rare Diseases, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Sch\u00e4ferhoff","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Witt","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theresia","family":"Zuleger","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-4836","authenticated-orcid":false,"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[{"name":"Centre for Rare Diseases, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Institute of Medical Genetics and Applied Genomics, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antje","family":"Bornemann","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, University Hospital T\u00fcbingen, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Alber","sequence":"additional","affiliation":[{"name":"Department of Neuropaediatrics, Developmental Neurology, Social Paediatrics, University Children\u2019s Hospital, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Ruf","sequence":"additional","affiliation":[{"name":"Department of Neuropaediatrics, Developmental Neurology, Social Paediatrics, University Children\u2019s Hospital, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ludger","family":"Schoels","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease, Hertie-Institute for Clinical Brain Research and Center for Neurology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Centre for Rare Diseases, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-911X","authenticated-orcid":false,"given":"Katarina","family":"Stingl","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology, University Eye Hospital, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-6227","authenticated-orcid":false,"given":"Nicole","family":"Weisschuh","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology, Institute for Ophthalmic Research, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/j.bbadis.2012.11.014","article-title":"Human pathology in NCL","volume":"1832","author":"Anderson","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1212\/WNL.0b013e31825f0547","article-title":"New nomenclature and classification scheme for the neuronal ceroid lipofuscinoses","volume":"79","author":"Williams","year":"2012","journal-title":"Neurology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/humu.21624","article-title":"Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses","volume":"33","author":"Kousi","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1016\/j.bbadis.2015.05.014","article-title":"Towards a new understanding of NCL pathogenesis","volume":"1852","author":"Cooper","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13024-018-0300-6","article-title":"Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses","volume":"14","author":"Mukherjee","year":"2019","journal-title":"Mol. Neurodegener."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"165570","DOI":"10.1016\/j.bbadis.2019.165570","article-title":"Pathomechanisms in the neuronal ceroid lipofuscinoses","volume":"1866","author":"Nelvagal","year":"2020","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1016\/j.bbadis.2013.05.014","article-title":"NCL disease mechanisms","volume":"1832","author":"Palmer","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1086\/518902","article-title":"The novel neuronal ceroid lipofuscinosis gene MFSD8 encodes a putative lysosomal transporter","volume":"81","author":"Siintola","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/MMBR.62.1.1-34.1998","article-title":"Major facilitator superfamily","volume":"62","author":"Pao","year":"1998","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1093\/hmg\/ddq381","article-title":"Expression and lysosomal targeting of CLN7, a major facilitator superfamily transporter associated with variant late-infantile neuronal ceroid lipofuscinosis","volume":"19","author":"Sharifi","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.nbd.2014.01.003","article-title":"Gene disruption of Mfsd8 in mice provides the first animal model for CLN7 disease","volume":"65","author":"Damme","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1093\/hmg\/ddv615","article-title":"Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7","volume":"25","author":"Brandenstein","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1093\/brain\/awn366","article-title":"Mutations in CLN7\/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis","volume":"132","author":"Kousi","year":"2009","journal-title":"Brain"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s10048-009-0185-1","article-title":"Neuronal ceroid lipofuscinosis caused by MFSD8 mutations: A common theme emerging","volume":"10","author":"Aldahmesh","year":"2009","journal-title":"Neurogenetics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.ejmg.2014.09.004","article-title":"Clinico-pathological manifestations of variant late infantile neuronal ceroid lipofuscinosis (vLINCL) caused by a novel mutation in MFSD8 gene","volume":"57","author":"Mandel","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kozina, A.A., Okuneva, E.G., Baryshnikova, N.V., Krasnenko, A.Y., Tsukanov, K.Y., Klimchuk, O.I., Kondakova, O.B., Larionova, A.N., Batysheva, T.T., and Surkova, E.I. (2018). A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: A case report. BMC Med. Genet., 19.","DOI":"10.1186\/s12881-018-0669-7"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s13256-018-1788-7","article-title":"Novel in-frame deletion in MFSD8 gene revealed by trio whole exome sequencing in an Iranian affected with neuronal ceroid lipofuscinosis type 7: A case report","volume":"12","author":"Garshasbi","year":"2018","journal-title":"J. Med. Case Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.ophtha.2014.07.040","article-title":"Mutations in MFSD8, encoding a lysosomal membrane protein, are associated with nonsyndromic autosomal recessive macular dystrophy","volume":"122","author":"Roosing","year":"2015","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1167\/iovs.16-20608","article-title":"Specific Alleles of CLN7\/MFSD8, a Protein That Localizes to Photoreceptor Synaptic Terminals, Cause a Spectrum of Nonsyndromic Retinal Dystrophy","volume":"58","author":"Khan","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1016\/j.ophtha.2017.04.008","article-title":"Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease","volume":"124","author":"Stone","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Birtel, J., Gliem, M., Mangold, E., M\u00fcller, P.L., Holz, F.G., Neuhaus, C., Lenzner, S., Zahnleiter, D., Betz, C., and Eisenberger, T. (2018). Next-generation sequencing identifies unexpected genotype-phenotype correlations in patients with retinitis pigmentosa. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0207958"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1080\/13816810.2019.1592200","article-title":"MFSD8 gene mutations; evidence for phenotypic heterogeneity","volume":"40","author":"Bushehri","year":"2019","journal-title":"Ophthalmic Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6684045","DOI":"10.1155\/2021\/6684045","article-title":"Novel MFSD8 Variants in a Chinese Family with Nonsyndromic Macular Dystrophy","volume":"2021","author":"Xiang","year":"2021","journal-title":"J. Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00439-017-1779-6","article-title":"The Human Gene Mutation Database: Towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies","volume":"136","author":"Stenson","year":"2017","journal-title":"Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nrg775","article-title":"Listening to silence and understanding nonsense: Exonic mutations that affect splicing","volume":"3","author":"Cartegni","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: The NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: Improving access to variant interpretations and supporting evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","article-title":"The mutational constraint spectrum quantified from variation in 141,456 humans","volume":"581","author":"Karczewski","year":"2020","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"1000 Genomes Project Consortium, Auton, A., Brooks, L.D., Durbin, R.M., Garrison, E.P., Kang, H.M., Korbel, J.O., Marchini, J.L., McCarthy, S., and McVean, G.A. (2015). A global reference for human genetic variation. Nature, 526, 68\u201374.","DOI":"10.1038\/nature15393"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1038\/s41467-019-10489-2","article-title":"A pan-cancer analysis of synonymous mutations","volume":"10","author":"Sharma","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2018.12.015","article-title":"Predicting Splicing from Primary Sequence with Deep Learning","volume":"176","author":"Jaganathan","year":"2019","journal-title":"Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0968-0004(00)01549-8","article-title":"Exonic splicing enhancers: Mechanism of action, diversity and role in human genetic diseases","volume":"25","author":"Blencowe","year":"2000","journal-title":"Trends Biochem. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.molcel.2006.05.018","article-title":"General and specific functions of exonic splicing silencers in splicing control","volume":"23","author":"Wang","year":"2006","journal-title":"Mol. Cell."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/humu.21458","article-title":"Prediction of single-nucleotide substitutions that result in exon skipping: Identification of a splicing silencer in BRCA1 exon 6","volume":"32","author":"Raponi","year":"2011","journal-title":"Hum. Mutat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1093\/bioinformatics\/btp124","article-title":"SpliceAid: A database of experimental RNA target motifs bound by splicing proteins in humans","volume":"25","author":"Piva","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1017\/S1355838200000960","article-title":"Sorting out the complexity of SR protein functions","volume":"6","author":"Graveley","year":"2000","journal-title":"RNA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1261\/rna.037044.112","article-title":"Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms","volume":"19","author":"Erkelenz","year":"2013","journal-title":"RNA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1126\/science.1073774","article-title":"Predictive identification of exonic splicing enhancers in human genes","volume":"297","author":"Fairbrother","year":"2002","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"D125","DOI":"10.1093\/nar\/gks997","article-title":"SpliceAid-F: A database of human splicing factors and their RNA-binding sites","volume":"41","author":"Giulietti","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/j.1651-2227.1988.tb10770.x","article-title":"Juvenile neuronal ceroid lipofuscinosis (JNCL): Quantitative description of its clinical variability","volume":"77","author":"Laabs","year":"1988","journal-title":"Acta Paediatr. Scand."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.2119\/molmed.2010.00241","article-title":"Analysis of potential biomarkers and modifier genes affecting the clinical course of CLN3 disease","volume":"17","author":"Lebrun","year":"2011","journal-title":"Mol. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s13760-021-01655-9","article-title":"A novel deletion variant in CLN3 with highly variable expressivity is responsible for juvenile neuronal ceroid lipofuscinoses","volume":"121","author":"Gilani","year":"2021","journal-title":"Acta Neurol. Belg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.bbrc.2008.12.159","article-title":"Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6","volume":"379","author":"Cannelli","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1002\/ana.410420517","article-title":"Clinical and magnetic resonance imaging findings in Batten disease: Analysis of the major mutation (1.02-kb deletion)","volume":"42","author":"Autti","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1007\/s100720070040","article-title":"Neuronal ceroid lipofuscinoses: Research update","volume":"21","author":"Wisniewski","year":"2000","journal-title":"Neurol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/usp.28.1.43.48","article-title":"The problematic issue of Kufs disease diagnosis as performed on rectal biopsies: A case report","volume":"28","author":"Pasquinelli","year":"2004","journal-title":"Ultrastruct. Pathol."},{"key":"ref_47","first-page":"109","article-title":"Adult neuronal ceroid-lipofuscinosis","volume":"8","author":"Goebel","year":"1989","journal-title":"Clin Neuropathol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Capalbo, A., Valero, R.A., Jimenez-Almazan, J., Pardo, P.M., Fabiani, M., Jim\u00e9nez, D., Simon, C., and Rodriguez, J.M. (2019). Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008409"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1093\/hmg\/8.10.1893","article-title":"Nonsense-mediated mRNA decay in health and disease","volume":"8","author":"Frischmeyer","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1212\/01.wnl.0000219042.60538.92","article-title":"Scale for the assessment and rating of ataxia: Development of a new clinical scale","volume":"66","author":"Baliko","year":"2006","journal-title":"Neurology"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Weisschuh, N., Mazzola, P., Heinrich, T., Haack, T., Wissinger, B., Tonagel, F., and Kelbsch, C. (2020). First submicroscopic inversion of the OPA1 gene identified in dominant optic atrophy\u2014A case report. BMC Med. Genet., 21.","DOI":"10.1186\/s12881-020-01166-z"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1101\/gr.229102","article-title":"The human genome browser at UCSC","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS Recommendations for the Description of Sequence Variants: 2016 Update","volume":"37","author":"Dalgleish","year":"2016","journal-title":"Hum. Mutat."},{"key":"ref_54","first-page":"751","article-title":"A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia","volume":"18","author":"Weisschuh","year":"2012","journal-title":"Mol. Vis."},{"key":"ref_55","first-page":"ddab286","article-title":"Mutations at a split codon in the GTPase-encoding domain of OPA1 cause dominant optic atrophy through different molecular mechanisms","volume":"24","author":"Weisschuh","year":"2021","journal-title":"Hum. Mol. Genet."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2271\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:22:22Z","timestamp":1760134942000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/4\/2271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,18]]},"references-count":55,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["ijms23042271"],"URL":"https:\/\/doi.org\/10.3390\/ijms23042271","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,18]]}}}