Ophthalmic Genetics最新文献

{"title":"Variable expressivity of the autosomal dominant vitreoretinochoroidopathy (ADVIRC) phenotype associated with a novel variant in <i>BEST1</i>.","authors":"Adam Mainguy, Claire Marie Dhaenens, Anais Poncet, Fanny Billaud, Lyse Giraud, Xavier Zanlonghi, Hélène Masse, Guylène Le Meur","doi":"10.1080/13816810.2024.2368797","DOIUrl":"10.1080/13816810.2024.2368797","url":null,"abstract":"<p><strong>Background: </strong>This case report explores the relationship between genetics and phenotypic variability in autosomal dominant vitreoretinochoroidopathy (ADVIRC). The study focuses on a case presenting a novel mutation in the <i>BEST1</i> gene and its phenotype in the case's relatives, shedding light on the structural and functional intricacies underlying this rare ophthalmologic disorder.</p><p><strong>Case presentation: </strong>A 33-year-old female presented for consultation with a history of bilateral retinal damage accompanied by a complaint of decreased visual acuity, progressive visual field deficit, and night blindness over the past year. Ophthalmic examination revealed a distinctive phenotype, including fibrillar vitreous, pigmented cells, and atrophic hyperpigmented retina in the periphery which was suggestive of a diagnosis of ADVIRC. Genetic testing revealed a heterozygous c.1101-1 G>T variant in <i>BEST1</i>, a novel splice site mutation. Functional analysis confirmed its impact on pre-mRNA splicing, resulting in an in-frame deletion (p(Ser367_Asn579del)). Family investigation revealed varying degrees of ophthalmologic impairment in the patient's mother and half-sister, both carrying the same mutation.</p><p><strong>Conclusions: </strong>This case report provides the first clinical description of the c.1101-1 G>T mutation in the <i>BEST1</i> gene associated with ADVIRC. The presence of intrafamilial variability, as evidenced by the differing clinical features observed in the index case and her half-sister, suggests the potential involvement of mechanisms influencing phenotype expression.<b>Abbreviation</b>: ADVIRC : autosomal dominant vitreoretinochoroidopathy; RNA : ribonucleic acid; RPE : retinal pigment epithelium.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"470-475"},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492869","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":"Novel <i>LOXL3</i>-associated stickler syndrome-like phenotype: a case report.","authors":"Adrianna E Klejnotowska, Megan Higgins, Shaheen P Shah","doi":"10.1080/13816810.2024.2369273","DOIUrl":"10.1080/13816810.2024.2369273","url":null,"abstract":"<p><strong>Purpose: </strong>To report the case of a young boy with early onset high myopia (eoHM), foveal hypoplasia and skeletal dysplasia due to a homozygous <i>LOXL3</i> pathogenic variant. Atypically, this was from a paternal uniparental isodisomy (UPiD) of chromosome 2.</p><p><strong>Clinical case: </strong>Four-year-old boy with several months history of holding items close to his face was found to have reduced visual acuity 6/30 in both eyes, bilateral vitreous syneresis, foveal hypoplasia and bilateral high myopia (-8.50D). A skeletal survey showed spondylo-epi-metaphyseal dysplasia. Whole-exome sequencing (WES) revealed a homozygous <i>LOXL3</i> variant c.1448_1449del, p.(Thr483Argfs*13), inherited through paternal UPiD of chromosome 2.</p><p><strong>Conclusion: </strong>To our knowledge, this is the first reported case of <i>LOXL3</i>-associated eoHM, foveal hypoplasia and mild skeletal dysplasia due to the rare phenomenon of paternal UPiD of chromosome 2. This case further delineates the phenotype associated with <i>LOXL3</i> pathogenic variants and supports truncating <i>LOXL3</i> pathogenic variants being associated with a phenotypic spectrum; from isolated eoHM through to a Stickler syndrome-like phenotype.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"476-480"},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492867","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":"Congenital Myasthenic Syndrome associated with acetylcholine receptor deficiency: case report and review of the literature.","authors":"Aashish Batheja, Julie Bayer-Vile, Evan Silverstein, Natario Couser","doi":"10.1080/13816810.2024.2352391","DOIUrl":"10.1080/13816810.2024.2352391","url":null,"abstract":"<p><strong>Introduction: </strong>Congenital Myasthenic Syndromes are a diverse group of conditions with a broad array of genetic underpinnings and phenotypic presentations. Acetylcholine receptor deficiency is one form that usually involves pathogenic variants in the Cholinergic Receptor Nicotinic Epsilon Subunit (<i>CHRNE</i>) gene encoding the ɛ-subunit of the acetylcholine receptor.</p><p><strong>Methods: </strong>We report a case of a 4-year-old male with suspected Congenital Myasthenic Syndrome with Acetylcholine Receptor Deficiency who presented with ocular symptoms and generalized muscle weakness. We additionally summarize published findings regarding the genetic, phenotypic, and clinical considerations of Congenital Myasthenic Syndrome with Acetylcholine Receptor Deficiency.</p><p><strong>Results: </strong>Exome sequencing revealed biallelic variants in <i>CHRNE</i> gene with a pathogenic frameshift variant and a variant of uncertain significance. After suboptimal response to pyridostigmine and albuterol, the patient experienced benefit with 3,4-DAP. The most commonly reported clinical characteristics in the literature are ptosis, muscle fatigability or weakness, and ophthalmoplegia.</p><p><strong>Conclusion: </strong>We present the case of a patient with biallelic variants in <i>CHRNE</i> gene including a variant of uncertain significance. Evaluation of variants of this gene, including the variant of uncertain significance identified in this case report, through further cases and studies may improve our understanding of Congenital Myasthenic Syndrome with Acetylcholine Receptor deficiency.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"481-487"},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238516","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 small deletion in <i>CWC27</i> gene associated with <i>CWC27</i>-related spliceosomeopathy.","authors":"Huajin Li, Kailing Zheng, Maosong Xie","doi":"10.1080/13816810.2024.2368791","DOIUrl":"10.1080/13816810.2024.2368791","url":null,"abstract":"<p><strong>Background: </strong><i>CWC27</i>-related spliceosomeopathy is a rare autosomal recessive disorder with only 14 patients have been reported. It is characterized by retinal degeneration, short stature, skeletal anomalies, and neurological defects. We described the clinical features of a Chinese patient with <i>CWC27</i>-related spliceosomeopathy and identified the pathogenic variant.</p><p><strong>Methods: </strong>The affected subject underwent detailed ophthalmic examinations. Systemic abnormalities were assessed, including body height, craniofacial morphology, oral cavity, hands, feet, hair and skin. Genomic DNA was isolated from peripheral blood and sequenced by next-generation sequencing. Sanger sequencing was performed for validation and segregation.</p><p><strong>Results: </strong>The patient had poor vision, nyctalopia and nystagmus from childhood. Fundoscopy revealed extensive chorioretinal atrophy with numerous scattered greyish pigmentation. Severe circular areas of macular atrophy were observed. Optical coherent tomography showed reduced retinal thickness with nearly absent ellipsoid zone and retinal pigment epithelium. In addition, craniofacial abnormalities, short statue, brachydactyly, dental anomalies, cafe-au-lait spots, scant hair, absent eyebrows and thin eyelashes were documented. Genetic analysis revealed a novel homozygous novel small deletion c.1133delG(p.G378Efs*12) in <i>CWC27</i> (NM_005869.2).</p><p><strong>Conclusions: </strong>We present a patient with early-onset retinitis pigmentosa and marked syndromic features. A novel <i>CWC27</i> pathogenic variant was identified. Our findings broaden the clinical and mutation spectrum of <i>CWC27</i>-related spliceosomeopathy, and could be helpful in diagnosis of this rare disease.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"537-541"},"PeriodicalIF":1.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492863","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 LAMP2 gene mimicking choroideremia carrier retinopathy","authors":"Akshay Narayan, Laura J. Taylor, Sian Sperring, Morag Shanks, Penny Clouston, Robert E. MacLaren, Jasmina Cehajic-Kapetanovic","doi":"10.1080/13816810.2024.2404148","DOIUrl":"https://doi.org/10.1080/13816810.2024.2404148","url":null,"abstract":"Danon disease is a rare, multisystemic X-linked dominant disorder caused by variants in the LAMP2 gene. It can be associated with retinal degeneration, but this is not well characterized. Here we d...","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":"31 1","pages":""},"PeriodicalIF":1.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264512","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":"BEST1 associated bestrophinopathies with angle closure and post-surgical malignant glaucoma.","authors":"Deepika C Parameswarappa,Jeyapoorani Balasubramnian,Srikanta Kumar Padhy,Saarang Hansraj,Ramya Natarajan,Chitra Kannabiran,Chandrasekhar Garudadri,Sirisha Senthil","doi":"10.1080/13816810.2024.2398827","DOIUrl":"https://doi.org/10.1080/13816810.2024.2398827","url":null,"abstract":"INTRODUCTIONMutations in BEST1 gene have been linked to the development of refractory angle closure glaucoma (ACG). This study aims to delineate the clinical characteristics, genetic mutations, and disease progression in patients with autosomal recessive bestrophinopathy (ARB) and autosomal dominant Best vitelliform macular dystrophy (BVMD) who are presented with treatment-resistant ACG.METHODSThis retrospective analysis encompasses a comprehensive ophthalmic assessment, retinal imaging, and mutational profiling of six patients diagnosed with bestrophinopathy and concurrent ACG, with a particular emphasis on the risk of post-glaucoma filtration surgery malignant glaucoma (MG). Exome sequencing was conducted utilizing a next-generation sequencing (NGS) based gene panel.RESULTSThe cohort included five patients with ARB and one with BVMD, with a mean (±SD) age at ACG diagnosis of 35.1 ± 6.9 years. NGS analysis revealed homozygous BEST1 variants in four patients (ARB; cases 1-4) and a heterozygous BEST1 variant in one patient (BVMD; case 5). One patient (ARB; case 6), despite a recessive pedigree, showed a single heterozygous variant, suggesting the presence of an undetected heterozygous variant indicative of compound heterozygous autosomal recessive inheritance. A novel non-frameshift deletion (c.841_843delTTC; p.Phe281del) was identified in case 2. Surgical intervention was required due to uncontrolled glaucoma in all cases except case 4. All five cases that underwent glaucoma filtration surgery developed MG, which was effectively managed with combined iridozonulo-hyaloido-vitrectomy (IZHV) and pars plana vitrectomy (PPV). Cases 5 and 6, harboring a heterozygous pathogenic variant (c.241 G>A; p.Val81Met), experienced refractory MG and corneal decompensation necessitating multiple interventions.CONCLUSIONGenomic analysis plays a pivotal role in the management of bestrophinopathies with ACG. Characterization of mutational types facilitates prognostication and enables timely interventions. IZHV with PPV emerges as a promising standalone or adjunctive procedure for the management of glaucoma among patients with BEST1 mutations and ACG.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":"31 1","pages":"1-12"},"PeriodicalIF":1.2,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180495","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 large multi-gene deletion in syndromic choroideremia.","authors":"Emily H Jung,Anna Duemler,Alessandro Iannaccone,Oleg Alekseev","doi":"10.1080/13816810.2024.2401850","DOIUrl":"https://doi.org/10.1080/13816810.2024.2401850","url":null,"abstract":"INTRODUCTIONCaused by mutation or deletion of the CHM gene, choroideremia is a rare X-linked recessive chorioretinal dystrophy characterized by progressive degeneration of the retinal pigment epithelium, photoreceptors, and the choriocapillaris. There are few published reports of choroideremia associated with complex syndromic phenotypes due to large or contiguous gene deletions.METHODSCase report and review of literature.RESULTSWe present a case of a 46-year-old male with a prior clinical diagnosis of syndromic retinitis pigmentosa, who was found to have syndromic choroideremia associated with a novel multi-gene deletion of 13.5 megabase pairs. This deletion encompassing 18 genes is one of the largest deletions reported in the literature. A total of 18 male cases of choroideremia associated with confirmed large or contiguous gene deletions have been published to date. Previously reported deletions range in size from 4 to 15 megabase pairs, and observed phenotypes include cleft lip and palate, ptosis, obesity, metabolic diseases, developmental delay, and hearing loss.DISCUSSIONThe contribution of our case aims to expand our understanding of Xq21 deletions and prompts further investigation of genes found in this locus. Furthermore, it highlights the importance of including syndromic choroideremia on the differential diagnosis in the workup of other syndromic retinopathies, particularly those that feature obesity, hearing loss, or intellectual disability.","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":"22 1","pages":"1-5"},"PeriodicalIF":1.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142180535","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":"Novel heterozygous <i>PRPH2</i> variant identified in a patient with spinocerebellar ataxia type 14 and macular dystrophy.","authors":"Tugche S Chen, Narin Sheri, David S Ehmann, Matthew D Benson","doi":"10.1080/13816810.2024.2321883","DOIUrl":"10.1080/13816810.2024.2321883","url":null,"abstract":"<p><strong>Purpose: </strong>To report on a patient with spinocerebellar ataxia type 14 (SCA14) and macular dystrophy with identification of a novel <i>PRPH2</i> variant.</p><p><strong>Methods: </strong>Case report.</p><p><strong>Results: </strong>A 63-year-old female with molecularly confirmed SCA14 presented with symmetric pigmentary disturbances in a perifoveal distribution resembling a pattern macular dystrophy. She had no history of using medications with recognized toxic macular effects. Subsequent genetic testing confirmed a novel heterozygous missense variant of unknown significance in <i>PRPH2</i> (<i>PRPH2</i>: c.694 G>A, p.(Ala232Thr)).</p><p><strong>Conclusions: </strong>To our knowledge, this is the first case of macular dystrophy identified in a patient with SCA14. While it is possible that the macular dystrophy observed in this patient might be an under-reported phenotype associated with SCA14, the pattern of macular changes is consistent with <i>PRPH2</i>-related disorders. The identified missense variant is predicted to be damaging by most in silico models, and the residue is highly conserved, adding support to a dual genetic diagnosis in this case.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"409-412"},"PeriodicalIF":1.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990831","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":"Primary congenital glaucoma in two siblings with different compound heterozygous CYP1B1 genotypes.","authors":"Alexandra Ruiz Guijosa, Laura Morales Fernández, José María Martínez de la Casa, Julio Escribano, Julián García Feijoo","doi":"10.1080/13816810.2024.2324044","DOIUrl":"10.1080/13816810.2024.2324044","url":null,"abstract":"<p><strong>Objective: </strong>To describe the inheritance pattern and clinical variability of primary congenital glaucoma (PCG) in a family with two affected siblings.</p><p><strong>Materials and methods: </strong>Two sisters diagnosed at birth with bilateral PCG, whose father had bilateral PCG and mother had bilateral microphthalmus, were subjected to a familial genetic study and ophthalmologic follow-up including intraocular pressure (IOP) measurement, and collection of biometric and cup-to-disc ratio data.</p><p><strong>Results: </strong>The inheritance pattern was autosomal recessive in compound heterozygosis. The sisters were found to be carriers of three pathogenic allele variants of the <i>CYP1B1</i> gene: <i>c.317C>A (p.Ala106Asp)</i> and <i>c.1345delG (p.Asp449MetfsTer8)</i> in one patient (10 years) and <i>c.1345delG (p.Asp449MetfsTer8)</i> and <i>c.202_209delCAGGCGGC (p.Gln68Serfs153Ter)</i> in her older sister (12 years). Surgical histories included: three goniotomies and two Ahmed valves in each eye, and two trabeculectomies and a pupilloplasty in the right eye in the 10-year old; and one goniotomy, trabeculectomy and three Ahmed valves in each eye in the older sister. Currently, both sisters have a controlled intraocular pressure of 18-20 mmHg in both eyes. The father is blind in both eyes and carries two variants <i>c.317C>A (p.Ala106Asp)</i> and <i>c.202_209delCAGGCGGC (p.Gln68Serfs153Ter)</i>. The mother with a single variant <i>c.1345delG (p.Asp440MetfsTer8)</i> has a prosthetic right eye and microphthalmus left eye.</p><p><strong>Conclusions: </strong>The sisters were found to show two different allelic CYP1B1 variants (compound heterozygosis) with different repercussions on the clinical severity of PCG. These findings highlight the importance of genetic screening of affected families.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"421-424"},"PeriodicalIF":1.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049992","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":"Variant in EZR leads to defects in lens development.","authors":"Nan Zhou, Mingyan He, Guangkai Zhou, Qiuyang Fan, Yanhua Qi","doi":"10.1080/13816810.2024.2330391","DOIUrl":"10.1080/13816810.2024.2330391","url":null,"abstract":"<p><strong>Background: </strong>Congenital cataract is a common cause of blindness. Genetic factors always play important role.</p><p><strong>Material and methods: </strong>This study identified a novel missense variant (c.1412C>T (p.P471L)) in the EZR gene in a four-generation Chinese family with nuclear cataract by linkage analysis and whole-exome sequencing. A knockout study in zebrafish using transcription activator-like effector nucleases was carried out to gain insight into candidate gene function.</p><p><strong>Results: </strong>Conservative and functional prediction suggests that the P-to-L substitution may impair the function of the human ezrin protein. Histology showed developmental delays in the ezrin-mutated zebrafish, manifesting as multilayered lens epithelial cells. Immunohistochemistry revealed abnormal proliferation patterns in mutant fish.</p><p><strong>Conclusions: </strong>The study suggests that ezrin may be involved in the enucleation and differentiation of lens epithelial cells.</p>","PeriodicalId":19594,"journal":{"name":"Ophthalmic Genetics","volume":" ","pages":"363-371"},"PeriodicalIF":1.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336373","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}