Ophthalmic Genetics最新文献

{"title":"Lack of genetic association of non-melanoma skin cancer and pseudoexfoliative glaucoma.","authors":"Alice A Beneke, Jon D Wiese, Kevin T Root, Kamil Taneja, Casey J Beal","doi":"10.1080/13816810.2024.2390008","DOIUrl":"10.1080/13816810.2024.2390008","url":null,"abstract":"<p><strong>Background: </strong>Prior research has shown a positive association of pseudoexfoliative glaucoma (PXG) in patients with non-melanoma skin cancer (NMSC), likely due to an increase in ultraviolet exposure associated with both. However, the role of NMSC as a genetic risk factor for PXG has not been examined. Thus, the goal of this study is to utilize Mendelian randomization with genome-wide association studies to evaluate for genetic causality while controlling for environmental confounders.</p><p><strong>Methods: </strong>We conducted a MR using the inverse variance weighted method (MR-IVW) as our primary analysis. Genomic data was sourced from GWASs for patients with NMSC (10,382 cases, 208,410 controls) and PXG (1,515 cases and 210,201 controls), originating from the FinnGen Biobank.</p><p><strong>Results: </strong>Despite previous association of history of NMSC with occurrence of PXG, we found no evidence for a causal association between SNPs associated with NMSC and risk of PXG following MR analysis (MR-IVW, odds ratio (OR): 0.98, 95% CI: 0.85-1.14, P = 0.87).</p><p><strong>Conclusion: </strong>Here, we found no evidence for a causal association between SNPs associated with NMSC and the risk of PXG following a MR analysis.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"623-625"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988549","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}

{"title":"Ophthalmic findings in Alström syndrome.","authors":"Yiyun Zhou, Tarek Saad Shoala, Antonie D Kline, Clair A Francomano, Mary Louise Z Collins, Marcia Ferguson, Jennifer Billiet, Janet S Sunness, Michelle Bianchi, Sharon Payne, Bin Guan, Sairah Yousaf, Alex V Levin","doi":"10.1080/13816810.2024.2402534","DOIUrl":"10.1080/13816810.2024.2402534","url":null,"abstract":"<p><strong>Importance: </strong>Alström syndrome is a rare genetic disorder characterized by retinopathy and has life-threatening complications. Alström syndrome is frequently misdiagnosed or confused with other early childhood disorders with retinopathy.  Understanding the spectrum of ocular manifestations of Alström syndrome is essential for ophthalmologists to recognize the cause and institute-appropriate care for this disorder that requires multidisciplinary attention.</p><p><strong>Objective: </strong>To quantify and summarize the common ocular findings of Alström syndrome.</p><p><strong>Design: </strong>Case series, clinical exam data obtained from 2015 to 2023.</p><p><strong>Setting: </strong>Semiannual multidisciplinary Alström syndrome clinics (2015-2023) at the Greater Baltimore Medical Center (GBMC), organized by Alström Syndrome International (ASI).</p><p><strong>Participants: </strong>Forty-eight patients (38 children, 10 adults) with a known diagnosis of Alström syndrome participated in the semiannual multidisciplinary Alström syndrome clinics. Patients apply to be seen and are accepted based on need and capacity.</p><p><strong>Intervention(s) or exposure(s): </strong>Not applicable.</p><p><strong>Main outcome(s) and measure(s): </strong>Clinical ocular findings.</p><p><strong>Results: </strong>Participants in this study had a median age of 8 years (15 months to 42 years). Visual acuity and progression of vision loss varied. The youngest patient who was legally blind was 2 years old. The oldest patient who maintained useful vision was 7 years old. All patients 8 years old or older were legally blind. Nystagmus (94%, 45 of 48) and photophobia (73%, 35 of 48) were the most common first presenting ocular symptoms in childhood. Retinal vascular attenuation (91%, 40 of 44) and retinal internal limiting membrane changes (68%, 30 of 44) were the most commonly documented retinal findings in both children and adults followed by optic nerve (ON) pallor and retinal pigment epithelium (RPE) mottling. Less than half of the children had ON pallor (38%, 14 of 37) and RPEmottling (38%, 14 of 37), while all adults had these two findings (100%, 7 of 7). Retinal pigment clumps were not common in children (11%, 4 of 37), while common in adults (86%, 6 of 7).</p><p><strong>Conclusions and relevance: </strong>Knowledge of these ocular findings is key to promptly recognize Alström syndrome. The ocular phenotype of Alström syndrome is largely dependent on age, suggesting that low vision interventions and potential gene-based therapeutics should target children with this disorder.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"596-601"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292797","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}

{"title":"A novel frameshift variant in <i>BCOR</i> causes congenital nuclear cataract.","authors":"Vanita Berry, Manav B Ponnekanti, Nikolas Pontikos, Roy A Quinlan, Michel Michaelides","doi":"10.1080/13816810.2024.2373248","DOIUrl":"10.1080/13816810.2024.2373248","url":null,"abstract":"<p><strong>Background: </strong>BCL6 co-repressor (<i>BCOR</i>) gene variants are involved in oculofaciocardiodental (OFCD) syndrome, acute myeloid leukaemia, renal tumours, and photoreceptor degenerative diseases. Here, we describe a British family with a pathogenic heterozygous variant in the <i>BCOR</i> gene causing congenital nuclear cataract.</p><p><strong>Methods: </strong>Whole-exome sequencing was conducted on an individual affected by X-linked dominant congenital cataract in a three-generation family to establish the underlying genetic basis. Bioinformatics analysis confirmed the variants with damaging pathogenicity scores.</p><p><strong>Results: </strong>A novel likely pathogenic frameshift variant <i>BCOR</i> NM_001123385.1: c.3621del; p.Lys1207AsnfsTer31, was identified and found to co-segregate with the disease in this family.</p><p><strong>Conclusions: </strong>This is apparently the first report of a variant in <i>BCOR</i> causing X-linked dominant congenital cataract which is potentially isolated or presenting with a remarkably mild systemic phenotype. Our findings extend the genetic basis for congenital cataract and add to the phenotypic spectrum of <i>BCOR</i> variants.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"591-595"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel <i>BBS1</i> deletion and <i>BBS9</i> nonsense pathogenic variant in Bardet-Biedl syndrome.","authors":"Janice Min Li, Erika Tavares, Jacque L Duncan, Ajoy Vincent, Elise Héon","doi":"10.1080/13816810.2024.2434039","DOIUrl":"https://doi.org/10.1080/13816810.2024.2434039","url":null,"abstract":"<p><strong>Background: </strong>Bardet-Biedl syndrome (BBS) is a rare syndromic ciliopathy characterized with retinal degeneration and a broad range of systemic features. Twenty-six BBS-associated genes have been identified to date and clinical genetic testing resolves around 80% of the cases. Two BBS cases unsolved by clinical genetic testing were recruited to identify causative variants using next-generation sequencing.</p><p><strong>Methods: </strong>Genomic DNA of the probands from both families was extracted from peripheral blood. Whole genome or exome sequencing results were analyzed with comprehensive variant filtering on structural variants, single nucleotide variants (SNVs), insertions/deletions (indels).</p><p><strong>Results: </strong>Family 1: A novel rare deletion NM_024649.5(<i>BBS1</i>): c.830 + 554_1110 + 1052del; p.(Asp278Metfs*3) was identified in the female proband in trans with a known pathogenic missense variant p.(Met390Arg). This 3k base pair (bp) deletion was predicted to cause a loss in exons 10-11, resulting in a premature stop codon. Family 2: Variant filtering in the male proband identified two rare (gnomAD AF < 0.01%) nonsense SNVs in trans in <i>BBS9</i>, NM_198428.3: c.724 G>T; p.(Gly242*) and c.966 G>A; p.(Trp322*), one of them being a novel pathogenic variant.</p><p><strong>Conclusion: </strong>All the novel variants identified fell into the pathogenic variant classification following ACMG/AMP criteria. This report highlights the role of whole exome and genome sequencing in unsolved cases.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"1-7"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770977","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}

{"title":"Atypical fundoscopic manifestation with good visual prognosis in familial hypomagnesemia with hypercalciuria and nephrocalcinosis.","authors":"M Girón-Ortega, M J Morillo Sánchez, M Soto-Sierra, M Mena, G Antinolo, M Ramos-Jiménez, M López-Domínguez, E Rodríguez-de-la-Rúa","doi":"10.1080/13816810.2024.2390021","DOIUrl":"10.1080/13816810.2024.2390021","url":null,"abstract":"<p><strong>Purpose: </strong>Pathogenic variants in the CLDN19 gene are responsible for Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) with ocular pathology (MIM *248190). Our objective was to delineate the ophthalmological and genetic manifestations of a patient with FHHNC and a pathogenic variant in <i>CLDN19</i>.</p><p><strong>Case report: </strong>A 25-year-old woman presented with renal involvement and a best-corrected visual acuity of 20/25 in the right eye and finger-counting ability in the left eye. The patient exhibited high myopia, convergent strabismus, and chorioretinal atrophic plaques in the perifoveal and peripapillary areas. We conducted a comprehensive ophthalmological examination, including refraction, fundoscopy, color and autofluorescence retinography, optical coherence tomography, and electrophysiology tests. Additionally, next-generation sequencing was performed using Illumina NextSeq500. We identified a homozygous missense variant, c.59G>A p.Gly20Asp, in the <i>CLDN19</i> gene as the cause of renal and ocular manifestations.</p><p><strong>Conclusion: </strong>FHHNC is associated with various ocular alterations. The unique retinal disorders described in this article suggest a more favorable visual prognosis compared to those previously reported in the literature. Determining the phenotypic diversity of this disease may aid in the diagnosis and management of future cases.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"663-667"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142110484","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}

{"title":"Bardet-Biedl syndrome with chorioretinal coloboma: a case series and review of literature.","authors":"Goura Chattannavar, Marina Ger, Jeyapoorani Balasubramanian, Sohini Mandal, Subhadra Jalali, Brijesh Takkar, Phattrawan Pisuchpen, Thales A C de Guimaraes, Jenina E Capasso, Srikanta Kumar Padhy, Alex V Levin","doi":"10.1080/13816810.2024.2411257","DOIUrl":"10.1080/13816810.2024.2411257","url":null,"abstract":"<p><strong>Introduction: </strong>Bardet-Biedl Syndrome (BBS) is a ciliopathy causing developmental defects and progressive retinal dystrophy, whereas choroidal coloboma is a developmental defect causing structural deficiency in the posterior retina. Both are rarely reported together.</p><p><strong>Methods: </strong>Here, we describe the phenotype and genotype of three unrelated patients with co-occurrence of Bardet-Biedl Syndrome and chorioretinal coloboma and review the pertinent literature.</p><p><strong>Results: </strong>We describe three unrelated patients, with variable clinical features of Bardet Biedl syndrome. None had family history of BBS or coloboma. Each carried biallelic variants in <i>BBS1</i>, <i>BBS9</i> and <i>TTC8</i> gene, respectively. Two had unilateral chorioretinal coloboma, while one had bilateral chorioretinal coloboma.</p><p><strong>Discussion: </strong>Although there may be other explanatory factors yet to be revealed, our data suggests that chorioretinal coloboma may be associated with BBS. The Hedgehog (Hh) signaling pathway, an intercellular communicator for development of the eye, is dependent on the primary cilia and plays a crucial role in the closure of the optic fissure. Both disorders therefore involve disruption of primary cilia function which may explain their association.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"616-622"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142471637","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}

{"title":"Monoallelic missense variants in <i>MAB21L1</i> cause a novel autosomal dominant microphthalmia.","authors":"Jinli Li, Qin Wang, Aijun Yang, Junyu Zhang","doi":"10.1080/13816810.2024.2378029","DOIUrl":"10.1080/13816810.2024.2378029","url":null,"abstract":"<p><strong>Purpose: </strong>The biallelic variant of <i>MAB21L1</i> has previously been documented in conjunction with the autosomal recessive cerebellar, ocular, craniofacial, and genital syndrome (COFG). The purpose of this study was to investigate the gene-disease association of <i>MAB21L1</i> and the newly discovered autosomal dominant (AD) microphthalmia.</p><p><strong>Methods: </strong>We report the presence of an exceptionally rare missense variant in a single allele of the Arg51 codon of <i>MAB21L1</i> among four individuals from a single family diagnosed with microphthalmia, which suggesting an autosomal dominant inheritance pattern. Subsequently, based on comprehensive literature review, we identified another 13 families that have reported cases of autosomal dominant microphthalmos.</p><p><strong>Results: </strong>Genotype-phenotype analysis revealed that patients with a single allele missense variant in <i>MAB21L1</i> exhibited solely eye abnormalities. This starkly diverged from the clinical presentation of COFG, typified by the concurrent occurrence of ocular and extraocular symptoms stemming from the biallelic variant in <i>MAB21L1</i>. Our findings revealed that the heterozygous pathogenic variant in <i>MAB21L1</i> resulted in the emergence of autosomal dominant microphthalmia. By combining these genetic and experimental evidence, the clinical validity of <i>MAB21L1</i> and the emerging autosomal dominant microphthalmia can be regarded as moderate.</p><p><strong>Conclusion: </strong>In summary, there is sufficient convincing evidence to prove that <i>MAB21L1</i> is a novel pathogenic gene responsible for autosomal dominant microphthalmia, thus offering valuable insights for precise diagnosis and targeted therapeutic interventions in cases of microphthalmia.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"650-656"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141627281","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}

{"title":"What have we learned about intraarterial chemotherapy (Ophthalmic Artery Chemosurgery) for retinoblastoma in the past 18 years? The third A. Linn Murphree Lecture.","authors":"David H Abramson","doi":"10.1080/13816810.2024.2388579","DOIUrl":"10.1080/13816810.2024.2388579","url":null,"abstract":"<p><p>Intraarterial chemotherapy (Ophthalmic Artery Chemosurgery/OAC) for retinoblastoma has transformed management of retinoblastoma worldwide since Pierre Gobin MD and I introduced it in 2006. Case reports, institutional series, meta-analyses, and randomized trials have validated its effectiveness and safety. It allows more eyes to be saved (at Memorial Sloan Kettering Cancer Center (MSKCC) as a result, we have gone from removing 96% of retinoblastoma eyes that presented with leukocoria (comparable to modern day International Classification \"D\" and \"E\" eyes) to saving 95% of these eyes with primary OAC management allows the majority of advanced intraocular eyes to be salvaged (both \"D\" and \"E\" eyes) prior to the chemoreduction era to saving 95% of these eyes with primary OAC management. OAC attains cures faster than intravenous protocols, has fewer systemic side effects, and is overall cheaper than intravenous approaches (because of the absence of side effects which are the main driver of cost in pediatric oncology). Unlike systemic chemotherapy no ports are needed (and no removal of ports for life threatening infections), it does not alter the immune system (so children can be immunized), it does not affect patient growth (and children who had received systemic chemotherapy catch up in growth during OAC), it does not affect hearing (which systemic Carboplatin does-especially in children <6 months of age), it eliminates the second cancers caused by radiation and systemic chemotherapy and does not compromise survival with all series showing patient survival >98%.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"551-557"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133394","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}

{"title":"Expanding the genotypic and phenotypic spectra with a novel variant in the ciliopathy gene, <i>CFAP410</i>, associated with selective cone degeneration.","authors":"Grace A Borchert, Morag E Shanks, Jennifer Whitfield, Penny Clouston, Shabnam Raji, Sian Sperring, Jennifer A Thompson, Kanmin Xue, Samantha R De Silva, Susan M Downes, Robert E MacLaren, Jasmina Cehajic-Kapetanovic","doi":"10.1080/13816810.2024.2369271","DOIUrl":"10.1080/13816810.2024.2369271","url":null,"abstract":"<p><strong>Background: </strong><i>CFAP410</i> (Cilia and Flagella Associated Protein 410) encodes a protein that has an important role in the development and function of cilia. In ophthalmology, pathogenic variants in <i>CFAP410</i> have been described in association with cone rod dystrophy, retinitis pigmentosa, with or without macular staphyloma, or with systemic abnormalities such as skeletal dysplasia and amyotrophic lateral sclerosis. Herein, we report a consanguineous family with a novel homozygous <i>CFAP410</i> c.335_346del variant with cone only degeneration and no systemic features.</p><p><strong>Methods: </strong>A retrospective analysis of ophthalmic history, examination, retinal imaging, electrophysiology and microperimetry was performed as well as genetic testing with <i>in silico</i> pathogenicity predictions and a literature review.</p><p><strong>Results: </strong>A systemically well 28-year-old female of Pakistani ethnicity with parental consanguinity and no relevant family history, presented with childhood-onset poor central vision and photophobia. Best-corrected visual acuity and colour vision were reduced (0.5 LogMAR, 6/17 Ishihara plates (right) and 0.6 LogMAR, 3/17 Ishihara plates (left). Fundus examination showed no pigmentary retinopathy, no macular staphyloma and autofluorescence was unremarkable. Optical coherence tomography showed subtle signs of intermittent disruption of the ellipsoid zone. Microperimetry demonstrated a reduction in central retinal sensitivity. Electrodiagnostic testing confirmed a reduction in cone-driven responses. Whole-genome sequencing identified an in-frame homozygous deletion of 12 base pairs at c.335_346del in <i>CFAP410</i>.</p><p><strong>Conclusions: </strong>The non-syndromic cone dystrophy phenotype reported herein expands the genotypic and phenotypic spectra of <i>CFAP410</i>-associated ciliopathies and highlights the need for light of potential future genetic therapies.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"633-639"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142133393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ectopia lentis associated with a 20-base deletion in the <i>ADAMTSL4</i> gene in the Old Order Amish population.","authors":"Grace Kuang, Baozhong Xin, Valerie Sency, Elias I Traboulsi, Vincent Cruz, Heng Wang","doi":"10.1080/13816810.2024.2406850","DOIUrl":"10.1080/13816810.2024.2406850","url":null,"abstract":"<p><strong>Background: </strong><i>ADAMTSL4</i>-related eye disorder is a rare autosomal recessive disease with a wide spectrum of severity and expressivity. We describe the genotypic and phenotypic findings in a cohort of Ohio Anabaptist with a pathogenic <i>ADAMTSL4</i> gene sequence variation.</p><p><strong>Methods: </strong>Patient phenotypes were gathered from clinical data. Genetic information was collected using clinical exome sequencing followed by Sanger sequencing.</p><p><strong>Results: </strong>Five patients from three Ohio Anabaptist families were determined to have a homozygous recessive <i>ADAMTSL4</i> 20-bp (c.767_786del) sequence variant. All five patients were found to have varying degrees of ectopia lentis and three patients presented with symptomatic lens subluxation. Average age of ectopia lentis diagnosis was 5 years (range 2-7 years). Additional features included persistent pupillary membrane and pupillary margin irregularities. The remaining two patients were asymptomatic and were found to have mild lens subluxation in adulthood, as they were examined following family genetic testing. Twenty-six heterozygous carriers were identified in a database of 1426 Ohio Old Order Amish individuals with an estimated carrier frequency of ~1:54 (allele frequency 0.91%).</p><p><strong>Discussion: </strong>This is the first study to identify an <i>ADAMTSL4</i> gene mutation in the Anabaptist population. Despite sharing the same genetic mutation, patients presented with a wide range of manifestations. A portion of affected individuals likely remain undiagnosed in the Anabaptist and general populations, especially if they are asymptomatic and only have mild lens subluxation. Implementation of early genetic screenings in high-risk populations can lead to improved awareness and patient outcomes.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"602-607"},"PeriodicalIF":1.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366070","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}