{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:07:46Z","timestamp":1780567666625,"version":"3.54.1"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T00:00:00Z","timestamp":1670457600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Biallelic pathogenic variants in the <jats:italic>neuroblastoma\u2010amplified sequence<\/jats:italic> (<jats:italic>NBAS<\/jats:italic>) gene manifest in a broad spectrum of disorders, including, but not limited to recurrent acute liver failure, skeletal dysmorphism, susceptibility to infections, and SOPH syndrome with its cardinal symptoms of short stature, optic atrophy, and Pelger\u2013Hu\u00ebt anomaly. We aimed to present clinical and genetic characteristics of two sisters (20 and 15\u2009years old) who were diagnosed with optic atrophy and cone dystrophy in childhood. Genome sequencing revealed two novel variants in <jats:italic>NBAS<\/jats:italic> in compound heterozygous state in both sisters, namely a 1\u2010bp deletion predicted to result in a premature termination codon (c.5104del; p.(Met1702*)), and a non\u2010canonical splice site variant of unclear significance (c.886\u20105T&gt;A; p.?).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Clinical examination and history revealed cone dystrophy, optic atrophy, and Pelger\u2013Hu\u00ebt anomaly, but no short stature, recurrent acute liver failure, or susceptibility to infections. RNA analysis revealed that the c.886\u20105T&gt;A variant results in two aberrant transcripts that are predicted to lead to in frame amino acid changes in the \u03b2\u2010propeller region of the protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We hypothesize that the phenotype of our subjects, which appears to be at the end of the spectrum of <jats:italic>NBAS<\/jats:italic>\u2010related disorders, could be explained by residual protein function mediated by the non\u2010canonical splice site variant c.886\u20105T&gt;A. Our study contributes to the existing knowledge on the genotypic and phenotypic spectrum of <jats:italic>NBAS<\/jats:italic>\u2010related disorders.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2120","type":"journal-article","created":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T14:19:58Z","timestamp":1670509198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Characterization of a novel non\u2010canonical splice site variant (c.886\u20105T&gt;A) in <i>NBAS<\/i> and description of the associated phenotype"],"prefix":"10.1002","volume":"11","author":[{"given":"Claudia S.","family":"Priglinger","sequence":"first","affiliation":[{"name":"University Eye Hospital, Ludwig Maximilians University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcnter","family":"Rudolph","sequence":"additional","affiliation":[{"name":"University Eye Hospital, Ludwig Maximilians University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Schmid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology and Oncology, Dr. von Hauner Children's Hospital University Hospital, Ludwig Maximilian University of Munich  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Mazzola","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias B.","family":"Haack","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics and Applied Genomics University of T\u00fcbingen  T\u00fcbingen Germany"},{"name":"Centre for Rare Diseases University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milda","family":"Reith","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology University Eye Hospital, University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarina","family":"Stingl","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology University Eye Hospital, University of T\u00fcbingen  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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  T\u00fcbingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e08\u201011\u20101104"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22981"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.05.009"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.12.015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20102308\u20107"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3319"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1153"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkt585"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.338061.120"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2009.074815"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaapos.2016.09.030"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaophthalmol.2020.5777"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/29.1.308"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436\u2010019\u20100698\u20104"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439\u2010017\u20101779\u20106"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2011.01.028"}],"container-title":["Molecular Genetics &amp; 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