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.

WDR34, a candidate gene for non-syndromic rod-cone dystrophy.

Rod-cone dystrophy (RCD), also called retinitis pigmentosa, is characterized by rod followed by cone photoreceptor degeneration, leading to gradual visual loss. Mutations in over 65 genes have been associated with non-syndromic RCD explaining 60% to 70% of cases, with novel gene defects possibly accounting for the unsolved cases. Homozygosity mapping and whole-exome sequencing applied to a case of autosomal recessive non-syndromic RCD from a consanguineous union identified a homozygous variant in WDR34. Mutations in WDR34 have been previously associated with severe ciliopathy syndromes possibly associated with a retinal dystrophy. This is the first report of a homozygous mutation in WDR34 associated with non-syndromic RCD.

Mutated CCDC51 Coding for a Mitochondrial Protein, MITOK Is a Candidate Gene Defect for Autosomal Recessive Rod-Cone Dystrophy.

The purpose of this work was to identify the gene defect underlying a relatively mild rod-cone dystrophy (RCD), lacking disease-causing variants in known genes implicated in inherited retinal disorders (IRD), and provide transcriptomic and immunolocalization data to highlight the best candidate. The DNA of the female patient originating from a consanguineous family revealed no large duplication or deletion, but several large homozygous regions. In one of these, a homozygous frameshift variant, c.244_246delins17 p.(Trp82Valfs*4); predicted to lead to a nonfunctional protein, was identified in CCDC51. CCDC51 encodes the mitochondrial coiled-coil domain containing 51 protein, also called MITOK. MITOK ablation causes mitochondrial dysfunction. Here we show for the first time that CCDC51/MITOK localizes in the retina and more specifically in the inner segments of the photoreceptors, well known to contain mitochondria. Mitochondrial proteins have previously been implicated in IRD, although usually in association with syndromic disease, unlike our present case. Together, our findings add another ultra-rare mutation implicated in non-syndromic IRD, whose pathogenic mechanism in the retina needs to be further elucidated.

The genetic landscape of inherited eye disorders in 74 consecutive families from the United Arab Emirates.

Genetic eye diseases are phenotypically and genetically heterogeneous, affecting 1 in 1,000 people worldwide. This prevalence can increase in populations where endogamy is a social preference, such as in Arab populations. A retrospective consecutive cohort of 91 patients from 74 unrelated families affected with non-syndromic and syndromic inherited eye disease presenting to the ocular genetics service at Moorfields Eye Hospitals United Arab Emirates (UAE) between 2017 and 2019, underwent clinically accredited genetic testing using targeted gene panels. The mean ± SD age of probands was 27.4 ± 16.2 years, and 45% were female (41/91). The UAE has a diverse and dynamic population, and the main ethnicity of families in this cohort was 74% Arab (n = 55), 8% Indian (n = 6) and 7% Pakistani (n = 5). Fifty-six families (90.3%) were genetically solved, with 69 disease-causing variants in 40 genes. Fourteen novel variants were detected with large deletions in CDHR1 and TTLL5, a multiexon (1-8) duplication in TEAD1 and 11 single nucleotides variants in 9 further genes. ABCA4-retinopathy was the most frequent cause accounting for 21% of cases, with the confirmed UAE founder mutation c.5882G>A p.(Gly1961Glu)/c.2570T>C p.(Leu857Pro) in 25%. High diagnostic yield for UAE patients can guide prognosis, family decision-making, access to clinical trials and approved treatments.

Whole exome sequencing resolves complex phenotype and identifies CC2D2A mutations underlying non-syndromic rod-cone dystrophy.

Genetic investigations were performed in three brothers from a consanguineous union, the two oldest diagnosed with rod-cone dystrophy (RCD), the youngest with early-onset cone-rod dystrophy and the two youngest with nephrotic-range proteinuria. Targeted next-generation sequencing did not identify homozygous pathogenic variant in the oldest brother. Whole exome sequencing (WES) applied to the family identified compound heterozygous variants in CC2D2A (c.2774G>C p.(Arg925Pro); c.4730_4731delinsTGTATA p.(Ala1577Valfs*5)) in the three brothers with a homozygous deletion in CNGA3 (c.1235_1236del p.(Glu412Valfs*6)) in the youngest correcting his diagnosis to achromatopsia plus RCD. None of the three subjects had cerebral abnormalities or learning disabilities inconsistent with Meckel-Gruber and Joubert syndromes, usually associated with CC2D2A mutations. Interestingly, an African woman with RCD shared the CC2D2A missense variant (c.2774G>C p.(Arg925Pro); with c.3182+355_3825del p.(?)). The two youngest also carried compound heterozygous variants in CUBN (c.7906C>T rs137998687 p.(Arg2636*); c.10344C>G p.(Cys3448Trp)) that may explain their nephrotic-range proteinuria. Our study identifies for the first time CC2D2A mutations in isolated RCD and underlines the power of WES to decipher complex phenotypes.

Prevalence of ABCA4 Deep-Intronic Variants and Related Phenotype in An Unsolved "One-Hit" Cohort with Stargardt Disease.

We investigated the prevalence of reported deep-intronic variants in a French cohort of 70 patients with Stargardt disease harboring a monoallelic pathogenic variant on the exonic regions of ABCA4. Direct Sanger sequencing of selected intronic regions of ABCA4 was conducted. Complete phenotypic analysis and correlation with the genotype was performed in case a known intronic pathogenic variant was identified. All other variants found on the analyzed sequences were queried for minor allele frequency and possible pathogenicity by in silico predictions. The second mutated allele was found in 14 (20%) subjects. The three known deep-intronic variants found were c.5196+1137G>A in intron 36 (6 subjects), c.4539+2064C>T in intron 30 (4 subjects) and c.4253+43G>A in intron 28 (4 subjects). Even though the phenotype depends on the compound effect of the biallelic variants, a genotype-phenotype correlation suggests that the c.5196+1137G>A was mostly associated with a mild phenotype and the c.4539+2064C>T with a more severe one. A variable effect was instead associated with the variant c.4253+43G>A. In addition, two novel variants, c.768+508A>G and c.859-245_859-243delinsTGA never associated with Stargardt disease before, were identified and a possible splice defect was predicted in silico. Our study calls for a larger cohort analysis including targeted locus sequencing and 3D protein modeling to better understand phenotype-genotype correlations associated with deep-intronic changes and patients' selection for clinical trials.

MERTK mutation update in inherited retinal diseases.

MER tyrosine kinase (MERTK) encodes a surface receptor localized at the apical membrane of the retinal pigment epithelium. It plays a critical role in photoreceptor outer segment internalization prior to phagocytosis. Mutations in MERTK have been associated with severe autosomal recessive retinal dystrophies in the RCS rat and in humans. We present here a comprehensive review of all reported MERTK disease causing variants with the associated phenotype. In addition, we provide further data and insights of a large cohort of 1,195 inherited retinal dystrophies (IRD) index cases applying state-of-the-art genotyping techniques and summarize current knowledge. A total of 79 variants have now been identified underlying rod-cone dystrophy and cone-rod dystrophy including 11 novel variants reported here. The mutation spectrum in MERTK includes 33 missense, 12 nonsense, 12 splice defects, 12 small deletions, two small insertion-deletions, three small duplications, and two exonic and three gross deletions. Altogether, mutations in MERTK account for ∼2% of IRD cases with a severe retinal phenotype. These data are important for current and future therapeutic trials including gene replacement therapy or cell-based therapy.

Expanding the Mutation Spectrum in ABCA4: Sixty Novel Disease Causing Variants and Their Associated Phenotype in a Large French Stargardt Cohort.

Here we report novel mutations in ABCA4 with the underlying phenotype in a large French cohort with autosomal recessive Stargardt disease. The DNA samples of 397 index subjects were analyzed in exons and flanking intronic regions of ABCA4 (NM_000350.2) by microarray analysis and direct Sanger sequencing. At the end of the screening, at least two likely pathogenic mutations were found in 302 patients (76.1%) while 95 remained unsolved: 40 (10.1%) with no variants identified, 52 (13.1%) with one heterozygous mutation, and 3 (0.7%) with at least one variant of uncertain significance (VUS). Sixty-three novel variants were identified in the cohort. Three of them were variants of uncertain significance. The other 60 mutations were classified as likely pathogenic or pathogenic, and were identified in 61 patients (15.4%). The majority of those were missense (55%) followed by frameshift and nonsense (30%), intronic (11.7%) variants, and in-frame deletions (3.3%). Only patients with variants never reported in literature were further analyzed herein. Recruited subjects underwent complete ophthalmic examination including best corrected visual acuity, kinetic and static perimetry, color vision test, full-field and multifocal electroretinography, color fundus photography, short-wavelength and near-infrared fundus autofluorescence imaging, and spectral domain optical coherence tomography. Clinical evaluation of each subject confirms the tendency that truncating mutations lead to a more severe phenotype with electroretinogram (ERG) impairment (p = 0.002) and an earlier age of onset (p = 0.037). Our study further expands the mutation spectrum in the exonic and flanking regions of ABCA4 underlying Stargardt disease.

Identification of a Novel Frameshift Variant in MYF5 Leading to External Ophthalmoplegia with Rib and Vertebral Anomalies.

Myogenic transcription factors with a basic helix-loop-helix (bHLH) such as MYOD, myogenin, MRF4, and MYF5 contribute to muscle differentiation and regulation. The MYF5 gene located on chromosome 12 encodes for myogenic factor 5 (MYF5), which has a role in skeletal and extraocular muscle development and rib formation. Variants in MYF5 were found to cause external ophthalmoplegia with rib and vertebral anomalies (EORVA), a rare recessive condition. To date, three homozygous variants in MYF5 have been reported to cause EORVA in six members of four unrelated families. Here, we present a novel homozygous MYF5 frameshift variant, c.596dupA p. (Asn199Lysfs*49), causing premature protein termination and presenting with external ophthalmoplegia, ptosis, and scoliosis in three siblings from a consanguineous family of Pakistani origin. With four MYF5 variants now discovered, genetic testing and paediatric assessment for extra-ocular features should be considered in all cases of congenital ophthalmoplegia.

The Genetic and Clinical Features of FOXL2-Related Blepharophimosis, Ptosis and Epicanthus Inversus Syndrome.

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) is a craniofacial disorder caused by heterozygous variants of the forkhead box L2 (FOXL2) gene. It shows autosomal dominant inheritance but can also occur sporadically. Depending on the mutation, two phenotypic subtypes have been described, both involving the same craniofacial features: type I, which is associated with premature ovarian failure (POF), and type II, which has no systemic features. The genotype-phenotype correlation is not fully understood, but it has been hypothesised that type I BPES involves more severe loss of function variants spanning the whole gene. Type II BPES has been linked to frameshift mutations that result in elongation of the protein rather than complete loss of function. A mutational hotspot has been identified within the poly-alanine domain, although the exact function of this region is still unknown. However, the BPES subtype cannot be determined genetically, necessitating informed genetic counselling and careful discussion of family planning advice in view of the associated POF particularly as the patient may still be a child. Following puberty, female patients should be referred for ovarian reserve and response assessment. Oculofacial features can be managed with surgical intervention and regular monitoring to prevent amblyopia.

Ocular Phenotype Associated with DYRK1A Variants.

Dual-specificity tyrosine phosphorylation-regulated kinase 1A or DYRK1A, contributes to central nervous system development in a dose-sensitive manner. Triallelic DYRK1A is implicated in the neuropathology of Down syndrome, whereas haploinsufficiency causes the rare DYRK1A-related intellectual disability syndrome (also known as mental retardation 7). It is characterised by intellectual disability, autism spectrum disorder and microcephaly with a typical facial gestalt. Preclinical studies elucidate a role for DYRK1A in eye development and case studies have reported associated ocular pathology. In this study families of the DYRK1A Syndrome International Association were asked to self-report any co-existing ocular abnormalities. Twenty-six patients responded but only 14 had molecular confirmation of a DYRK1A pathogenic variant. A further nineteen patients from the UK Genomics England 100,000 Genomes Project were identified and combined with 112 patients reported in the literature for further analysis. Ninety out of 145 patients (62.1%) with heterozygous DYRK1A variants revealed ocular features, these ranged from optic nerve hypoplasia (13%, 12/90), refractive error (35.6%, 32/90) and strabismus (21.1%, 19/90). Patients with DYRK1A variants should be referred to ophthalmology as part of their management care pathway to prevent amblyopia in children and reduce visual comorbidity, which may further impact on learning, behaviour, and quality of life.

Generation of two human iPSC lines from patients with autosomal dominant retinitis pigmentosa (UCLi014-A) and autosomal recessive Leber congenital amaurosis (UCLi015-A), associated with RDH12 variants.

Induced pluripotent stem cell (iPSC) lines were generated from two patients with RDH12 variants. UCLi014-A is from a patient with heterozygous frameshift mutation c.759del p.(Phe254Leufs*24), associated with autosomal dominant retinitis pigmentosa. UCLi015-A is from a patient with homozygous missense mutation c.619A > G p.(Asn207Asp), associated with Leber congenital amaurosis. Fibroblasts were derived from skin biopsies and reprogrammed using integration free episomal reprogramming plasmids. The iPSC lines expressed pluripotency markers, exhibited differentiation potential in vitro and displayed normal karyotypes. These cell lines will act as a tool for disease modelling, enabling comparison of disease mechanisms, identification of therapeutic targets and drug screening.

Generation of human iPSC line (UCLi013-A) from a patient with microphthalmia and aniridia, carrying a heterozygous missense mutation c.372C>A p.(Asn124Lys) in PAX6.

A human induced pluripotent stem cell (hiPSC) line (UCLi013-A) was generated from fibroblast cells of a 34-year-old donor with multiple ocular conditions including severe microphthalmia and aniridia. The patient had a heterozygous missense mutation in PAX6 c.372C>A, p.(Asn124Lys), validated in the fibroblasts through Sanger sequencing. Fibroblasts derived from a skin biopsy were reprogrammed using integration free episomal reprogramming. The established iPSC line was found to express pluripotency markers, exhibit differentiation potential in vitro and display a normal karyotype. This cell line will act as a tool for disease modelling of microphthalmia and aniridia, identification of therapeutic targets and drug screening.

A Novel Splice-Site Variant in CACNA1F Causes a Phenotype Synonymous with Åland Island Eye Disease and Incomplete Congenital Stationary Night Blindness.

BACKGROUND: CACNA1F-related disorders encompass progressive and non-progressive disorders, including Åland island eye disease and incomplete congenital stationary night blindness. These two X-linked disorders are characterized by nystagmus, color vision defect, myopia, and electroretinography (ERG) abnormalities. Ocular hypopigmentation and iris transillumination are reported only in patients with Åland island eye disease. Around 260 variants were reported to be associated with these two non-progressive disorders, with 19 specific to Åland island eye disease and 14 associated with both Åland island eye disease and incomplete congenital stationary night blindness. CACNA1F variants spread on the gene and further analysis are needed to reveal phenotype-genotype correlation. CASE REPORT: A complete ocular exam and genetic testing were performed on a 13-year-old boy. A novel splice-site variant, c.4294-11C>G in intron 36 in CACNA1F, was identified at hemizygous state in the patient and at heterozygous state in his asymptomatic mother and explained the phenotype synonymous with Åland island eye disease and incomplete congenital stationary night blindness observed in the patient. CONCLUSION: We present a novel variant in the CACNA1F gene causing phenotypic and electrophysiologic findings indistinguishable from those of AIED/CSNB2A disease. This finding further expands the mutational spectrum and our knowledge of CACNA1F-related disease.

Retinal Phenotype of Patients With Isolated Retinal Degeneration Due to CLN3 Pathogenic Variants in a French Retinitis Pigmentosa Cohort.

Importance: Biallelic variants in CLN3 lead to a spectrum of diseases, ranging from severe neurodegeneration with retinal involvement (juvenile neuronal ceroid lipofuscinosis) to retina-restricted conditions. Objective: To provide a detailed description of the retinal phenotype of patients with isolated retinal degeneration harboring biallelic CLN3 pathogenic variants and to attempt a phenotype-genotype correlation associated with this gene defect. Design, Setting, and Participants: This retrospective cohort study included patients carrying biallelic CLN3 variants extracted from a cohort of patients with inherited retinal disorders (IRDs) investigated at the National Reference Center for Rare Ocular Diseases of the Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts from December 2007 to August 2020. Data were analyzed from October 2019 to August 2020. Main Outcome and Measures: Functional (best-corrected visual acuity, visual field, color vision, and full-field electroretinogram), morphological (multimodal retinal imaging), and clinical data from patients were collected and analyzed. Gene defect was identified by either next-generation sequencing or whole-exome sequencing and confirmed by Sanger sequencing, quantitative polymerase chain reaction, and cosegregation analysis. Results: Of 1533 included patients, 843 (55.0%) were women and 690 (45.0%) were men. A total of 15 cases from 11 unrelated families harboring biallelic CLN3 variants were identified. All patients presented with nonsyndromic IRD. Two distinct patterns of retinal disease could be identified: a mild rod-cone degeneration of middle-age onset (n = 6; legal blindness threshold reached by 70s) and a severe retinal degeneration with early macular atrophic changes (n = 9; legal blindness threshold reached by 40s). Eleven distinct pathogenic variants were detected, of which 4 were novel. All but 1, p.(Arg405Trp), CLN3 point variants and their genotypic associations were clearly distinct between juvenile neuronal ceroid lipofuscinosis and retina-restricted disease. Mild and severe forms of retina-restricted CLN3-linked IRDs also had different genetic background. Conclusions and Relevance: These findings suggest CLN3 should be included in next-generation sequencing panels when investigating patients with nonsyndromic rod-cone dystrophy. These results document phenotype-genotype correlations associated with specific variants in CLN3. However, caution seems warranted regarding the potential neurological outcome if a pathogenic variant in CLN3 is detected in a case of presumed isolated IRD for the onset of neurological symptoms could be delayed.

Practical guide to genetic screening for inherited eye diseases.

Genetic eye diseases affect around one in 1000 people worldwide for which the molecular aetiology remains unknown in the majority. The identification of disease-causing gene variant(s) allows a better understanding of the disorder and its inheritance. There is now an approved retinal gene therapy for autosomal recessive RPE65-retinopathy, and numerous ocular gene/mutation-targeted clinical trials underway, highlighting the importance of establishing a genetic diagnosis so patients can fully access the latest research developments and treatment options. In this review, we will provide a practical guide to managing patients with these conditions including an overview of inheritance patterns, required pre- and post-test genetic counselling, different types of cytogenetic and genetic testing available, with a focus on next generation sequencing using targeted gene panels, whole exome and genome sequencing. We will expand on the pros and cons of each modality, variant interpretation and options for family planning for the patient and their family. With the advent of genomic medicine, genetic screening will soon become mainstream within all ophthalmology subspecialties for prevention of disease and provision of precision therapeutics.

Generation of two human control iPS cell lines (UCLi016-A and UCLi017-A) from healthy donors with no known ocular conditions.

Two human induced pluripotent stem cell (hiPSC) lines (UCLi016-A and UCLi017-A) were generated from fibroblast cells of 23- and 34-year-old healthy male donors with no known ocular conditions. Fibroblast cells were derived from skin biopsies and reprogrammed using integration free episomal reprogramming. The established iPSC lines were found to express pluripotency markers, exhibit differentiation potential in vitro and display a normal karyotype. These cell lines will act as a control lines for researchers studying ocular diseases.

Peripapillary Sparing With Near Infrared Autofluorescence Correlates With Electroretinographic Findings in Patients With Stargardt Disease.

Purpose: To evaluate the correlation between the quantification of peripapillary sparing and electroretinogram (ERG) outcomes in autosomal recessive Stargardt disease (STGD1). Methods: Near infrared fundus autofluorescence (NIR-FAF) images of 101 eyes of 101 patients were retrospectively reviewed. Peripapillary sparing was assessed both qualitatively and quantitatively. The area of spared tissue (AST) was calculated in a 1-mm-wide ring around the optic disc after binarization of the 55° NIR-FAF. These measurements were correlated with the presence of normal ERG (group I), abnormal photopic responses (group II), or abnormal photopic and scotopic responses (group III). Results: AST showed significant correlations with ERG groups (R = -0.802, P < 0.001). While qualitative assessment of peripapillary sparing (i.e., present or not) also showed a significant correlation with ERG groups (R = -0.435, P < 0.001), it was weaker than by AST quantification. The ordinal regression analysis showed that the increase in AST was associated with a decrease in the odds of belonging to ERG groups II and III, with an odds ratio of 0.82 (95% confidence interval [CI] 0.78-0.87), P < 0.001. Conclusions: The AST around the optic disc in eyes with STGD1 correlates with the impairment of photoreceptors as shown in the ERG. If replicated in future longitudinal studies, the quantification of peripapillary sparing may prove to be a useful parameter for evaluating the visual prognosis of these eyes.

Longitudinal Clinical Follow-up and Genetic Spectrum of Patients With Rod-Cone Dystrophy Associated With Mutations in PDE6A and PDE6B.

Importance: A precise phenotypic characterization of retinal dystrophies is needed for disease modeling as a basis for future therapeutic interventions. Objective: To compare genotype, phenotype, and structural changes in patients with rod-cone dystrophy (RCD) associated with mutations in PDE6A or PDE6B. Design, Setting, and Participants: In a retrospective cohort study conducted in Paris, France, from January 2007 to September 2017, 54 patients from a cohort of 1095 index patients with RCD underwent clinical examination, including personal and familial history, best-corrected visual acuity (BCVA), color vision, slitlamp examination, full-field electroretinography, kinetic visual fields (VFs), retinophotography, optical coherence tomography, near-infrared fundus autofluorescence, and short-wavelength fundus autofluorescence imaging. Genotyping was performed using microarray analysis, targeted next-generation sequencing, and Sanger sequencing validation with familial segregation when possible. Data were analyzed from September 1, 2017, to February 1, 2018. Clinical variables were subsequently analyzed in 2018. Main Outcomes and Measures: Phenotype and genotype comparison of patients carrying mutations in PDE6A or PDE6B. Results: Of the 54 patients included in the study, 19 patients of 17 families (11 women [58%]; mean [SD] age at diagnosis, 14.83 [10.63] years) carried pathogenic mutations in PDE6A, and 35 patients of 26 families (17 women [49%]; mean [SD] age at diagnosis, 21.10 [11.56] years) had mutations in PDE6B, accounting for prevalences of 1.6% and 2.4%, respectively. Among 49 identified genetic variants, 14 in PDE6A and 15 in PDE6B were novel. Overall, phenotypic analysis revealed no substantial differences between the 2 groups except for night blindness as a presenting symptom that was noted to be more prevalent in the PDE6A than PDE6B group (80% vs 37%, respectively; P = .005). The mean binocular BCVA and VF decrease over time (measured as mean individual slopes coefficients) was comparable between patients with PDE6A and PDE6B mutations: 0.04 (0.12) vs 0.02 (0.05) for BCVA (P = .89) and 14.33 (7.12) vs 13.27 (6.77) for VF (P = .48). Conclusions and Relevance: Mutations in PDE6A and PDE6B accounted for 1.6% and 2.4%, respectively, in a cohort of French patients with RCD. The functional and structural findings reported may constitute the basis of disease modeling that might be used for better prognostic estimation and candidate selection for photoreceptor therapeutic rescue.

Generation of human induced pluripotent stem cell lines from a patient with ITM2B-related retinal dystrophy and a non mutated brother.

Human induced pluripotent stem cell (iPSC) lines were generated from fibroblasts of a patient affected with an autosomal dominant retinal dystrophy carrying the mutation c.782A>C, p.Glu261Ala in ITM2B and from an unaffected brother. Three different iPSC lines were generated and characterized from primary dermal fibroblasts of the affected subject and two from the unaffected brother. All iPSC lines expressed the pluripotency markers, were able to differentiate into the three germ layers and presented normal karyotypes. This cellular model will provide a powerful tool to study this retinal dystrophy and better understand the role of ITM2B.