Ophthalmic Genetics最新文献

NRL-associated autosomal recessive retinopathy: novel variants expanding the phenotype, natural history and a comprehensive literature search. nrl相关的常染色体隐性视网膜病变：扩大表型的新变体，自然史和全面的文献检索。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-15 DOI: 10.1080/13816810.2025.2559705

Marium Raza, Elisa E Cornish, Chris Ovens, Benjamin M Nash, Julie McGaughran, Robyn V Jamieson, John R Grigg

{"title":"NRL-associated autosomal recessive retinopathy: novel variants expanding the phenotype, natural history and a comprehensive literature search.","authors":"Marium Raza, Elisa E Cornish, Chris Ovens, Benjamin M Nash, Julie McGaughran, Robyn V Jamieson, John R Grigg","doi":"10.1080/13816810.2025.2559705","DOIUrl":"https://doi.org/10.1080/13816810.2025.2559705","url":null,"abstract":"Background: Neural retina leucine zipper (NRL) is a crucial transcription factor that plays a key role in the development and differentiation of photoreceptor cells. A variant in this gene can cause a retinal phenotype known as Enhanced S cone Syndrome (ESCS). This study presents three novel autosomal recessive (ar) NRL variants and expands the clinical ophthalmic phenotype of NRL-associated retinopathy to include microphthalmia.Methods: Investigations included electrodiagnostic testing, best corrected visual acuity (BCVA), optical coherence tomography (OCT), ultra-wide field autofluorescence (UWAF), fundus imaging, and visual fields. PubMed, Cochrane library and ClinVar database were used for literature search.Results: Three patients (P1-3) from 2 different families with novel biallelic NRL variants were reported. P1 had novel homozygous likely-pathogenic NRL variant, p.(Glu86*). Genetic screening of both P2 and P3 identified a second and third novel heterozygous likely pathogenic variants, p.(Leu75Profs *19) and p.(Ser6Alafs *13). Multimodal imaging and functional studies in these patients were consistent with the classical features of ESCS with an additional feature of microphthalmia.Conclusion: This study expands the genotype and phenotype of NRL-associated retinopathy and compares the ocular phenotype of our cohort with published NRL reports in the literature.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-13"},"PeriodicalIF":1.0,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145302405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Choroidal neovascularization in a teenager with Kearns Sayre syndrome. 卡恩斯·塞尔综合征青少年脉络膜新生血管的形成。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-14 DOI: 10.1080/13816810.2025.2572711

Miriam Ehrenberg, Assaf Dotan, Orly Gal-Or, Gad Dotan, Rita Ehrlich, Amir Sternfeld

{"title":"Choroidal neovascularization in a teenager with Kearns Sayre syndrome.","authors":"Miriam Ehrenberg, Assaf Dotan, Orly Gal-Or, Gad Dotan, Rita Ehrlich, Amir Sternfeld","doi":"10.1080/13816810.2025.2572711","DOIUrl":"https://doi.org/10.1080/13816810.2025.2572711","url":null,"abstract":"Background: Kearns Sayre syndrome (KSS) is a rare multisystem mitochondrial disorder. KSS primarily targets energy supply in cells through impaired oxidative metabolism and reduced ATP (Adenosine triphosphate) production. KSS is clinically characterized by a classic triad of chronic progressive external ophthalmoplegia, retinitis pigmentosa and cardiac conduction defect. Additional features may include neurological abnormalities, endocrinopathies, renal disease, growth failure, myopathy and more.Materials and methods: We present a case of a young male with KSS, retinal dystrophy and multiple systemic abnormalities.Results: Despite treatment with three intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, the CNV demonstrated limited response and progressive enlargement, leading to poor final visual outcome.Conclusion: To our knowledge, CNV has not been previously documented in Kearns -Sayre syndrome. This report underscores the need for ongoing surveillance in patients with rare retinal dystrophies, given the potential for unforeseen complications.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-2"},"PeriodicalIF":1.0,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-09 DOI: 10.1080/13816810.2025.2572708

Abhishek Das, Ponny J Kumar, Parag K Shah, Narendran Venkatapathy

{"title":"KIF11-related MCLMR presenting with FEVR-like retinopathy: first report in an Indian child.","authors":"Abhishek Das, Ponny J Kumar, Parag K Shah, Narendran Venkatapathy","doi":"10.1080/13816810.2025.2572708","DOIUrl":"https://doi.org/10.1080/13816810.2025.2572708","url":null,"abstract":"Introduction: KIF11 gene mutations can result in a rare autosomal dominant inheritable disease called microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR/MLCRD). Recently, such mutations were also found to be associated with familial exudative vitreoretinopathy (FEVR).Methods: Retrospective case report.Results: A 2-month-old female child came to our clinic for fundus evaluation. On examination, there was microcephaly with dysmorphism of broad and bulbous nose and bilateral pitting edema. Fundus examination revealed bilateral symmetrical chorio-retinal atrophic spots with dysplasia and temporal peripheral avascular retina. Fluorescein angiography revealed peripheral avascular retina without any neovascularisation elsewhere. Whole genome sequencing along with mitochondrial genome sequencing revealed a heterozygous, likely pathogenic, mutation in KIF11 c.2830C > T (pArg944Cys) (Transcript: NM_004523.4) in exon 20 with an inheritance of autosomal dominant confirming the diagnosis of KIF11-related Retinopathy.Conclusion: Genetic counseling and family screening are paramount for managing this multisystem disorder and advising on recurrence risk. Genetic testing confirmed the KIF11 mutation, providing insights into the management and prognosis.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-4"},"PeriodicalIF":1.0,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145258700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel missense TUBB4B variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss. 典型热点外的一种新的错义TUBB4B变体与锥杆营养不良和感音神经性听力损失有关。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-07 DOI: 10.1080/13816810.2025.2565651

Lauren Y Cao, Anna Duemler, Emily H Jung, Ramiro S Maldonado, Sarah Richards, Elena R Schiff, Omar A Mahroo, Andrew R Webster, Siying Lin, Beau J Fenner, Alessandro Iannaccone, Oleg Alekseev

{"title":"A novel missense TUBB4B variant outside of the canonical hotspot is associated with cone-rod dystrophy and sensorineural hearing loss.","authors":"Lauren Y Cao, Anna Duemler, Emily H Jung, Ramiro S Maldonado, Sarah Richards, Elena R Schiff, Omar A Mahroo, Andrew R Webster, Siying Lin, Beau J Fenner, Alessandro Iannaccone, Oleg Alekseev","doi":"10.1080/13816810.2025.2565651","DOIUrl":"https://doi.org/10.1080/13816810.2025.2565651","url":null,"abstract":"Introduction: Pathogenic variants in TUBB4B, which encodes the β-tubulin 4B isotype of microtubule subunits, have been associated with Leber congenital amaurosis with early-onset deafness (LCAEOD), an autosomal dominant condition characterized by early and severe loss of photoreceptor and cochlear cells. The majority of reported cases feature early disease onset and are caused by missense mutations in the R390/R391 hotspot.Methods: Multimodal evaluation included ultra-widefield pseudocolor and autofluorescence fundus photography, spectral-domain optical coherence tomography, full-field electroretinography, Goldmann kinetic perimetry, audiography, and genetic testing with next-generation sequencing.Results: We report seven individuals from three unrelated families affected by cone-rod dystrophy and sensorineural hearing loss associated with a novel variant in TUBB4B (c.784C > T, p.R262W). Cone-rod dystrophy associated with this variant generally features a later age of onset compared to the Leber congenital amaurosis caused by variants in the canonical hotspot.Discussion: This report expands the mutation spectrum and phenotypic range of TUBB4B-associated retinopathies beyond the R390/R391 hotspot and may offer insight into the pathogenesis of this rare tubulinopathy.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-10"},"PeriodicalIF":1.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Measuring historical variant reclassification in inherited retinal disease and its impact on clinical genetic testing. 测量遗传性视网膜疾病的历史变异重分类及其对临床基因检测的影响。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-07 DOI: 10.1080/13816810.2025.2568002

Karly Kern, Adam Gordon, Andy Drackley, Jennifer Rossen, Valerie Allegretti, Sharon Aufox, Alexander Ing

{"title":"Measuring historical variant reclassification in inherited retinal disease and its impact on clinical genetic testing.","authors":"Karly Kern, Adam Gordon, Andy Drackley, Jennifer Rossen, Valerie Allegretti, Sharon Aufox, Alexander Ing","doi":"10.1080/13816810.2025.2568002","DOIUrl":"https://doi.org/10.1080/13816810.2025.2568002","url":null,"abstract":"Introduction: Inherited retinal diseases (IRDs) are clinically and genetically diverse conditions whose heterogeneity makes molecular diagnosis challenging. These challenges can lead to interpretation discordance which has a particular impact on gene-targeted therapies for IRD.Methods: Discordance was evaluated in a clinical testing cohort and in ClinVar. 140 sequence variants identified through genetic testing in a cohort of pediatric participations with IRD were reclassified using the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines for variant interpretation. ClinVar datasets from December 2, 2019 and January 3, 2022 for the gene RPE65 were analyzed for discordance.Results: The discordance rate in the pediatric cohort was 22.2%. Discordance in ClinVar increased from 23.6% to 36.6%.Discussion: Discordance in the pediatric cohort may have been impacted by subjective application of the ACMG/AMP guidelines and heterogeneity in IRD. Subjectivity in the guidelines, laboratory differences, and lack of interpretation review may have contributed to discordance in ClinVar. Work to improve interpretation for IRD should include better understanding of the genetic influences of IRD and optimization of the ACMG/AMP guidelines for this field.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.0,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Long-read sequencing uncovers novel pathogenic duplications in the PRPH2 gene in patients with macular dystrophy. 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。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-05 DOI: 10.1080/13816810.2025.2568004

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":"Long-read sequencing uncovers novel pathogenic duplications in the PRPH2 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":"https://doi.org/10.1080/13816810.2025.2568004","url":null,"abstract":"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.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-8"},"PeriodicalIF":1.0,"publicationDate":"2025-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Membrane frizzled-related protein: a comprehensive analysis of genetic characteristics, phenotypic manifestations and impact on retinal microvasculature. 膜卷曲相关蛋白：遗传特征、表型表现及对视网膜微血管影响的综合分析。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-02 DOI: 10.1080/13816810.2025.2566428

Metehan Simsek, Merve Ozbek, Selim Ayata, Oguzhan Yarali, Yusuf Alperen Yarali, Ozgur Artunay

{"title":"Membrane frizzled-related protein: a comprehensive analysis of genetic characteristics, phenotypic manifestations and impact on retinal microvasculature.","authors":"Metehan Simsek, Merve Ozbek, Selim Ayata, Oguzhan Yarali, Yusuf Alperen Yarali, Ozgur Artunay","doi":"10.1080/13816810.2025.2566428","DOIUrl":"https://doi.org/10.1080/13816810.2025.2566428","url":null,"abstract":"Purpose: To assess the ocular characteristics, retinal microvasculature, and long-term outcomes of patients with nanophthalmos associated with mutations in the membrane frizzled-related protein (MFRP) gene, and to compare these findings with those observed in nanophthalmos cases without MFRP gene mutations.Methods: In this retrospective cohort study, patients with MFRP-associated nanophthalmos and those with nanophthalmos without MFRP gene mutations were included. Best-corrected visual acuity (BCVA), spherical equivalent (SE), axial length (AL), optical coherence tomography (OCT), and OCT angiography parameters-including vascular density (VD) and foveal avascular zone (FAZ) measurements in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC)-were evaluated at presentation and at the 5th-year follow-up.Results: At presentation and 5-year follow-up, patients with MFRP-associated nanophthalmos exhibited significantly shorter AL and higher SE compared to those without MFRP mutations (all p < 0.001). Central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and retinal nerve fiber layer (RNFL) thickness were significantly greater in the MFRP-associated group at presentation and 5-year follow-up (all p < 0.05). OCT angiography revealed reduced parafoveal VD in the SCP and DCP, as well as decreased foveal and parafoveal VD in the CC in the MFRP group compared to the group without MFRP mutations (all p < 0.05). FAZ areas in the SCP and DCP were also significantly smaller in the MFRP group (p < 0.001 and p = 0.01, respectively).Conclusions: Eyes with MFRP-associated nanophthalmos exhibit significantly higher SE, shorter AL, and more pronounced alterations in retinal structure and microvasculature compared with eyes without MFRP mutations.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-10"},"PeriodicalIF":1.0,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring copy number variations in Lebanese families with rod-cone dystrophy reveals a novel deletion in PRPF31 with haploinsufficiency. 探索黎巴嫩杆状锥体营养不良家庭的拷贝数变化揭示了PRPF31单倍不足的新缺失。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-01 Epub Date: 2025-04-28 DOI: 10.1080/13816810.2025.2495945

Zahraa Mousawi, Maysa Choukeir, Lama Jaffal, Louna Karam, Alexandre Assi, José-Noel Ibrahim, Alain Chebly, Said El Shamieh

{"title":"Exploring copy number variations in Lebanese families with rod-cone dystrophy reveals a novel deletion in PRPF31 with haploinsufficiency.","authors":"Zahraa Mousawi, Maysa Choukeir, Lama Jaffal, Louna Karam, Alexandre Assi, José-Noel Ibrahim, Alain Chebly, Said El Shamieh","doi":"10.1080/13816810.2025.2495945","DOIUrl":"10.1080/13816810.2025.2495945","url":null,"abstract":"Background and objectives: Rod-cone dystrophy (RCD), also known as retinitis pigmentosa, is the most common group of retinal dystrophies, affecting around 1:4,000 individuals worldwide. In the present work, we performed a copy number variation (CNV) analysis on next-generation sequencing (NGS) data from two Lebanese families with RCD, since no disease-causing mutations were identified through the analysis of single nucleotide variants (SNVs) and insertions/deletions (Indels). NGS, real-time PCR (qPCR), and chromosomal microarray were performed to identify, validate, and delineate the causative CNVs identified in both families involved in this study. Additionally, expression analysis using qPCR and western blotting was conducted to assess the effect of the PRPF31 variant on gene and protein expression levels.Results: A novel heterozygous deletion (701 bp) spanning exons 6 and 7 of PRPF31 was identified in the first family (F11), resulting in autosomal dominant RCD due to haploinsufficiency. This was confirmed by reduced mRNA levels and the complete absence of protein expression in the affected individuals (F11:III.2 and F11:II.2). In the second family (F26), we identified a previously documented homozygous deletion in the exons 3-19 of MERTK gene, which is responsible for causing severe autosomal recessive RCD.Conclusion: The current study expands the mutational spectrum of PRPF31 and MERTK genes, underscoring the importance of CNVs and haploinsufficiency in RCD etiology. These findings serve as a foundation for future analyses concerning gene augmentation therapies.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"440-446"},"PeriodicalIF":1.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-01 Epub Date: 2025-05-25 DOI: 10.1080/13816810.2025.2503387

Goura Chattannavar, Celeste S Wyman, Eran Tallis, Alexandra Hubbel, Laura Rohan, Lindsay Adamczak, David N Korones, Vikas Khetan

{"title":"PMS2-related constitutional mismatch repair deficiency in a patient with unilateral retinoblastoma and negative germline RB1.","authors":"Goura Chattannavar, Celeste S Wyman, Eran Tallis, Alexandra Hubbel, Laura Rohan, Lindsay Adamczak, David N Korones, Vikas Khetan","doi":"10.1080/13816810.2025.2503387","DOIUrl":"10.1080/13816810.2025.2503387","url":null,"abstract":"Background: Retinoblastoma, the primary ocular tumor in childhood, arises from the photoreceptor cells of the retina caused by pathogenic loss-of-function variants in both alleles of the RB1 gene, which can be either germline or somatic. The predisposition to hereditary retinoblastoma is primarily linked to germline variants in the RB1 gene.Material and methods: Here, we describe a two-year-old girl from a Mennonite community who presented at 6 months of age with unilateral Group E retinoblastoma and underwent enucleation. She had a strong family history of cancer: a third elder sister deceased at age 4 with concurrent Burkitt lymphoma and medulloblastoma, and father diagnosed with carcinoid tumor at age 27.Results: RB1 gene testing detected two pathogenic variants in the RB1 gene (c.299dup, c.1959del) in the tumor tissue. These variants were not identified in blood, indicating somatic changes. Testing of 49 genes associated with cancer predisposition identified a germline homozygous likely pathogenic variant in PMS2 (c.2095 G>T, p.Asp699His) in the proband, consistent with the diagnosis of constitutional mismatch repair deficiency (CMMRD). The proband's fourth elder sister who also tested homozygous for the PMS2 variant, was diagnosed with low grade glioma identified during screening as a part of surveillance for CMMRD.Conclusions: This case highlights the importance of considering CMMRD in retinoblastoma with normal germline RB1 sequence, particularly with additional factors like family cancer history, consanguinity, or multiple childhood malignancies. Given retinoblastoma's association with CMMRD, screening for it in children with CMMRD is recommended.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"479-482"},"PeriodicalIF":1.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pseudocolobomatous autosomal dominant atrophic maculopathy (PADAM). 假性结肠瘤性常染色体显性萎缩性黄斑病（PADAM）。

IF 1 4区医学

Ophthalmic Genetics Pub Date : 2025-10-01 Epub Date: 2025-05-25 DOI: 10.1080/13816810.2025.2492045

Jonathan Hensman, Mary J van Schooneveld, Roselie M H Diederen, Astrid S Plomp, Cansu de Muijnck, Jacoline B Ten Brink, Ralph J Florijn, Elfride de Baere, Maria M van Genderen, Camiel J F Boon

{"title":"Pseudocolobomatous autosomal dominant atrophic maculopathy (PADAM).","authors":"Jonathan Hensman, Mary J van Schooneveld, Roselie M H Diederen, Astrid S Plomp, Cansu de Muijnck, Jacoline B Ten Brink, Ralph J Florijn, Elfride de Baere, Maria M van Genderen, Camiel J F Boon","doi":"10.1080/13816810.2025.2492045","DOIUrl":"10.1080/13816810.2025.2492045","url":null,"abstract":"Purpose: To describe a family with a previously unreported maculopathy across three generations.Methods: This retrospective chart study describes three patients from three generations of a non-consanguineous Dutch family, with a distinctive maculopathy. All three patients underwent extensive ophthalmic examinations and multimodal imaging including best-corrected visual acuity, fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence imaging, and full-field electroretinography (ffERG). Genetic analyses included next-generation sequencing, whole-exome sequencing, and single nucleotide polymorphism arrays.Results: Three affected family members had a history of low visual acuity and congenital nystagmus, in combination with sharply demarcated areas of chorioretinal atrophy in the macula, which developed from early childhood. The two adult patients who underwent ffERG had cone and rod responses within normal limits, suggesting a central condition with a normally functioning retina extending beyond the lesions. No (likely) pathogenic variants in the known disease associated genes were found through extensive genetic analysis.Conclusion: Pseudocolobomatous autosomal dominant atrophic maculopathy (PADAM) is a striking hereditary maculopathy that leads to progressive central vision loss. Future studies may provide additional insights into the genetic basis and underlying mechanisms of this remarkable clinical picture.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"468-473"},"PeriodicalIF":1.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0