Michael P Backlund, Suzie A Gasparian, Pauliina E Repo, Harri Kangas, Kati Donner, Heidi Putkuri, Sanna Seitsonen, Maarjaliis Paavo, Tero T Kivelä, David I Sierpina, Joni A Turunen
{"title":"长读测序揭示了黄斑营养不良患者中PRPH2基因的新致病性重复。","authors":"Michael P Backlund, Suzie A Gasparian, Pauliina E Repo, Harri Kangas, Kati Donner, Heidi Putkuri, Sanna Seitsonen, Maarjaliis Paavo, Tero T Kivelä, David I Sierpina, Joni A Turunen","doi":"10.1080/13816810.2025.2568004","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Clinical variability and incomplete penetrance characterize retinal dystrophies associated with <i>PRPH2</i> gene variants. Here, we utilized adaptive nanopore long-read sequencing (LRS) to solve a genetic diagnosis for dominantly inherited macular dystrophies in two families.</p><p><strong>Methods: </strong>Patient 1 (P1) and her daughter, Patient 2 (P2) were clinically evaluated using multimodal imaging and electrophysiological testing at Helsinki University Hospital, Finland, and Patient 3 (P3) from a different family, at Loma Linda University, USA. The patients were subjected to retinal dystrophy gene panels and the suspected duplications were characterized with nanopore LRS.</p><p><strong>Results: </strong>P1 presented with butterfly-shaped pattern dystrophy (BPD) and P2 with vitelliform macular dystrophy. P3 showed BPD in the right eye and late-stage BPD in the left. Gene panels suggested that the patients shared the same heterozygous 482 bp <i>PRPH2</i> exon 2 duplication. LRS revealed the duplications to be almost 4kb in size with breakpoints (BP) in intronic Alu-elements. In P1 and P2, the 3'BP resides within a novel Alu-element. The duplication has not been reported earlier and is missing from the gnomAD database.</p><p><strong>Conclusion: </strong>This study presents novel <i>PRPH2</i> exon 2 duplications associated with macular dystrophies.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.0000,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Long-read sequencing uncovers novel pathogenic duplications in the <i>PRPH2</i> gene in patients with macular dystrophy.\",\"authors\":\"Michael P Backlund, Suzie A Gasparian, Pauliina E Repo, Harri Kangas, Kati Donner, Heidi Putkuri, Sanna Seitsonen, Maarjaliis Paavo, Tero T Kivelä, David I Sierpina, Joni A Turunen\",\"doi\":\"10.1080/13816810.2025.2568004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Clinical variability and incomplete penetrance characterize retinal dystrophies associated with <i>PRPH2</i> gene variants. Here, we utilized adaptive nanopore long-read sequencing (LRS) to solve a genetic diagnosis for dominantly inherited macular dystrophies in two families.</p><p><strong>Methods: </strong>Patient 1 (P1) and her daughter, Patient 2 (P2) were clinically evaluated using multimodal imaging and electrophysiological testing at Helsinki University Hospital, Finland, and Patient 3 (P3) from a different family, at Loma Linda University, USA. The patients were subjected to retinal dystrophy gene panels and the suspected duplications were characterized with nanopore LRS.</p><p><strong>Results: </strong>P1 presented with butterfly-shaped pattern dystrophy (BPD) and P2 with vitelliform macular dystrophy. P3 showed BPD in the right eye and late-stage BPD in the left. Gene panels suggested that the patients shared the same heterozygous 482 bp <i>PRPH2</i> exon 2 duplication. LRS revealed the duplications to be almost 4kb in size with breakpoints (BP) in intronic Alu-elements. In P1 and P2, the 3'BP resides within a novel Alu-element. The duplication has not been reported earlier and is missing from the gnomAD database.</p><p><strong>Conclusion: </strong>This study presents novel <i>PRPH2</i> exon 2 duplications associated with macular dystrophies.</p>\",\"PeriodicalId\":19594,\"journal\":{\"name\":\"Ophthalmic Genetics\",\"volume\":\" \",\"pages\":\"1-8\"},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2025-10-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ophthalmic Genetics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/13816810.2025.2568004\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ophthalmic Genetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/13816810.2025.2568004","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
摘要
目的:临床变异性和不完全外显性表征与PRPH2基因变异相关的视网膜营养不良。在这里,我们利用自适应纳米孔长读测序(LRS)来解决两个家族中显性遗传性黄斑营养不良症的基因诊断。方法:患者1 (P1)和她的女儿,患者2 (P2)在芬兰赫尔辛基大学医院通过多模式成像和电生理测试进行临床评估,患者3 (P3)来自不同的家庭,在美国洛马林达大学。对患者进行视网膜营养不良基因检测,并用纳米孔LRS对可疑的重复基因进行表征。结果:P1表现为蝴蝶状营养不良(BPD), P2表现为卵黄样黄斑营养不良。P3显示右眼BPD,左眼晚期BPD。基因面板显示患者共享相同的杂合482 bp PRPH2外显子2重复。LRS显示,在内含子alu元素中,带有断点(BP)的重复大小接近4kb。在P1和P2中,3'BP位于一个新的alu元素中。之前没有报告重复,并且在gnomAD数据库中丢失了重复。结论:本研究发现了与黄斑营养不良相关的新型PRPH2外显子2重复。
Long-read sequencing uncovers novel pathogenic duplications in the PRPH2 gene in patients with macular dystrophy.
Purpose: Clinical variability and incomplete penetrance characterize retinal dystrophies associated with PRPH2 gene variants. Here, we utilized adaptive nanopore long-read sequencing (LRS) to solve a genetic diagnosis for dominantly inherited macular dystrophies in two families.
Methods: Patient 1 (P1) and her daughter, Patient 2 (P2) were clinically evaluated using multimodal imaging and electrophysiological testing at Helsinki University Hospital, Finland, and Patient 3 (P3) from a different family, at Loma Linda University, USA. The patients were subjected to retinal dystrophy gene panels and the suspected duplications were characterized with nanopore LRS.
Results: P1 presented with butterfly-shaped pattern dystrophy (BPD) and P2 with vitelliform macular dystrophy. P3 showed BPD in the right eye and late-stage BPD in the left. Gene panels suggested that the patients shared the same heterozygous 482 bp PRPH2 exon 2 duplication. LRS revealed the duplications to be almost 4kb in size with breakpoints (BP) in intronic Alu-elements. In P1 and P2, the 3'BP resides within a novel Alu-element. The duplication has not been reported earlier and is missing from the gnomAD database.
Conclusion: This study presents novel PRPH2 exon 2 duplications associated with macular dystrophies.
期刊介绍:
Ophthalmic Genetics accepts original papers, review articles and short communications on the clinical and molecular genetic aspects of ocular diseases.