Christina Zeitz , Julien Navarro , Leila Azizzadeh Pormehr , Cécile Méjécase , Luiza M. Neves , Camille Letellier , Christel Condroyer , Shahad Albadri , Andréa Amprou , Aline Antonio , Tasnim Ben-Yacoub , Juliette Wohlschlegel , Camille Andrieu , Malo Serafini , Lorenzo Bianco , Alessio Antropoli , Marco Nassisi , Said El Shamieh , Sandra Chantot-Bastaraud , Saddek Mohand-Saïd , Isabelle Audo
{"title":"UBAP1L 变异导致常染色体隐性杆-锥-杆营养不良症","authors":"Christina Zeitz , Julien Navarro , Leila Azizzadeh Pormehr , Cécile Méjécase , Luiza M. Neves , Camille Letellier , Christel Condroyer , Shahad Albadri , Andréa Amprou , Aline Antonio , Tasnim Ben-Yacoub , Juliette Wohlschlegel , Camille Andrieu , Malo Serafini , Lorenzo Bianco , Alessio Antropoli , Marco Nassisi , Said El Shamieh , Sandra Chantot-Bastaraud , Saddek Mohand-Saïd , Isabelle Audo","doi":"10.1016/j.gim.2024.101081","DOIUrl":null,"url":null,"abstract":"<div><h3>Purpose</h3><p>Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian descent with only few reports of North African descent.</p></div><div><h3>Methods</h3><p>Genome, targeted next-generation, and Sanger sequencing was applied to cohort of ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium cells, and zebrafish. Variants’ pathogenicity was accessed using 3D-modeling and/or ROs.</p></div><div><h3>Results</h3><p>Here, we identified a novel gene defect with three distinct pathogenic variants in <em>UBAP1L</em> in 4 independent autosomal recessive IRD cases from Tunisia. <em>UBAP1L</em> is expressed in the retinal pigment epithelium and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin-associated domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the solenoid of overlapping ubiquitin-associated domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein.</p></div><div><h3>Conclusion</h3><p>Biallelic <em>UBAP1L</em> variants are a novel cause of IRDs, most likely enriched in the North African population.</p></div>","PeriodicalId":12717,"journal":{"name":"Genetics in Medicine","volume":null,"pages":null},"PeriodicalIF":6.6000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1098360024000145/pdfft?md5=33acc92b25da13257c9c33f4bb9e974a&pid=1-s2.0-S1098360024000145-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy\",\"authors\":\"Christina Zeitz , Julien Navarro , Leila Azizzadeh Pormehr , Cécile Méjécase , Luiza M. Neves , Camille Letellier , Christel Condroyer , Shahad Albadri , Andréa Amprou , Aline Antonio , Tasnim Ben-Yacoub , Juliette Wohlschlegel , Camille Andrieu , Malo Serafini , Lorenzo Bianco , Alessio Antropoli , Marco Nassisi , Said El Shamieh , Sandra Chantot-Bastaraud , Saddek Mohand-Saïd , Isabelle Audo\",\"doi\":\"10.1016/j.gim.2024.101081\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><p>Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian descent with only few reports of North African descent.</p></div><div><h3>Methods</h3><p>Genome, targeted next-generation, and Sanger sequencing was applied to cohort of ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium cells, and zebrafish. Variants’ pathogenicity was accessed using 3D-modeling and/or ROs.</p></div><div><h3>Results</h3><p>Here, we identified a novel gene defect with three distinct pathogenic variants in <em>UBAP1L</em> in 4 independent autosomal recessive IRD cases from Tunisia. <em>UBAP1L</em> is expressed in the retinal pigment epithelium and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin-associated domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the solenoid of overlapping ubiquitin-associated domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein.</p></div><div><h3>Conclusion</h3><p>Biallelic <em>UBAP1L</em> variants are a novel cause of IRDs, most likely enriched in the North African population.</p></div>\",\"PeriodicalId\":12717,\"journal\":{\"name\":\"Genetics in Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.6000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S1098360024000145/pdfft?md5=33acc92b25da13257c9c33f4bb9e974a&pid=1-s2.0-S1098360024000145-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetics in Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1098360024000145\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics in Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1098360024000145","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Variants in UBAP1L lead to autosomal recessive rod-cone and cone-rod dystrophy
Purpose
Progressive inherited retinal degenerations (IRDs) affecting rods and cones are clinically and genetically heterogeneous and can lead to blindness with limited therapeutic options. The major gene defects have been identified in subjects of European and Asian descent with only few reports of North African descent.
Methods
Genome, targeted next-generation, and Sanger sequencing was applied to cohort of ∼4000 IRDs cases. Expression analyses were performed including Chip-seq database analyses, on human-derived retinal organoids (ROs), retinal pigment epithelium cells, and zebrafish. Variants’ pathogenicity was accessed using 3D-modeling and/or ROs.
Results
Here, we identified a novel gene defect with three distinct pathogenic variants in UBAP1L in 4 independent autosomal recessive IRD cases from Tunisia. UBAP1L is expressed in the retinal pigment epithelium and retina, specifically in rods and cones, in line with the phenotype. It encodes Ubiquitin-associated protein 1-like, containing a solenoid of overlapping ubiquitin-associated domain, predicted to interact with ubiquitin. In silico and in vitro studies, including 3D-modeling and ROs revealed that the solenoid of overlapping ubiquitin-associated domain is truncated and thus ubiquitin binding most likely abolished secondary to all variants identified herein.
Conclusion
Biallelic UBAP1L variants are a novel cause of IRDs, most likely enriched in the North African population.
期刊介绍:
Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health.
GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.