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Burstedt, Marie
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Publications (10 of 32) Show all publications
Kvanta, A., Rangaswamy, N., Holopigian, K., Watters, C., Jennings, N., Liew, M. S. H., . . . André, H. (2024). Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial. Nature Communications, 15(1), Article ID 7438.
Open this publication in new window or tab >>Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial
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2024 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 15, no 1, article id 7438Article in journal (Refereed) Published
Abstract [en]

Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.

Place, publisher, year, edition, pages
Springer Nature, 2024
National Category
General Practice
Identifiers
urn:nbn:se:umu:diva-229644 (URN)10.1038/s41467-024-51575-4 (DOI)001335554500014 ()2-s2.0-85203422763 (Scopus ID)
Available from: 2024-09-16 Created: 2024-09-16 Last updated: 2025-04-24Bibliographically approved
Whelan, J., Green, J., Burstedt, M., Greco, E., Ni, X., Spera, C., . . . Holopigian, K. (2024). Patient-reported outcomes in RLBP1 retinal dystrophy: longitudinal assessment in a prospective natural history study. Translational Vision Science & Technology, 13(11), Article ID 16.
Open this publication in new window or tab >>Patient-reported outcomes in RLBP1 retinal dystrophy: longitudinal assessment in a prospective natural history study
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2024 (English)In: Translational Vision Science & Technology, E-ISSN 2164-2591, Vol. 13, no 11, article id 16Article in journal (Refereed) Published
Abstract [en]

Purpose: To evaluate the performance of two non-disease-specific patient-reported outcome (PRO) instruments, the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and the Low Luminance Questionnaire (LLQ), in patients with retinaldehyde-binding protein 1 retinal dystrophy (RLBP1 RD).

Methods: PROs were assessed using the VFQ-25 and LLQ. Rasch analysis was conducted to estimate person and item measures of the VFQ-25 and LLQ questionnaires to determine the association between the two PROs. In addition, the association between these two instruments and their correlations to weighted measures of visual function and disease progression were analyzed in this three-year PRO-focused sub-study of a five-year prospective natural history study.

Results: Forty-two patients participated, with most of them having completed at least two PRO follow-up visits at least one year apart. The mean VFQ-25 scores were lowest for distance activities (39.2-49.0) and peripheral vision (37.5-52.4), with mean LLQ subscale scores generally low (<41), except for the emotional distress subscale. Using Rasch analysis, calibrated item and person measures along with their standard errors were estimated for both ePROs. This indicated that the distribution of the VFQ-25 and LLQ item measures well covered the distribution of person function in this group. This suggests that the item difficulties well cover the person-level performance in this population. As well, the two PROs showed a strong and significant correlation at all assessed time points as assessed with Pearson correlation coefficient (0.81, 0.91, 0.81 and 0.87 at baseline, 1/1.5, 2/2.5 (P < 0.001) and 3/3.5 years (P = 0.002)). The composite scores of both PRO questionnaires strongly correlated with clinical measures of visual function. At 2 to 2.5 years of follow-up, meaningful statistically significant declines in peripheral vision (both VFQ-25 and LLQ), distance vision (VFQ-25), and extreme lighting in dark and bright light (LLQ) subscales were noted.

Conclusions: This study demonstrated a strong association between VFQ-25 and LLQ scores and their association with clinical measures of visual function.

Translational Relevance: PRO instruments can provide insights into the specific disabilities of this unique patient population and help to guide appropriate outcome measures for future clinical trials.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology (ARVO), 2024
Keywords
low luminance questionnaire, national eye institute visual function questionnaire, patient-reported outcomes, quality of life, retinaldehyde-binding protein 1 (RLBP1), retinal dystrophy, visual function
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:umu:diva-232150 (URN)10.1167/tvst.13.11.16 (DOI)39541109 (PubMedID)2-s2.0-85209402205 (Scopus ID)
Available from: 2024-12-04 Created: 2024-12-04 Last updated: 2024-12-04Bibliographically approved
Whelan, J., Green, J., Burstedt, M., Greco, E., Ni, X., Spera, C., . . . Holopigian, K. (2024). Patient-reported outcomes in RLBP1 retinal dystrophy: longitudinal assessment in a prospective natural history study. Translational Vision Science & Technology, 13(11), 1-14, Article ID 16.
Open this publication in new window or tab >>Patient-reported outcomes in RLBP1 retinal dystrophy: longitudinal assessment in a prospective natural history study
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2024 (English)In: Translational Vision Science & Technology, E-ISSN 2164-2591, Vol. 13, no 11, p. 1-14, article id 16Article in journal (Refereed) Published
Abstract [en]

Purpose: To evaluate the performance of two non-disease–specific patient-reported outcome (PRO) instruments, the National Eye Institute Visual Function Questionnaire-25 (VFQ-25) and the Low Luminance Questionnaire (LLQ), in patients with retinaldehyde-binding protein 1 retinal dystrophy (RLBP1 RD).

Methods: PROs were assessed using the VFQ-25 and LLQ. Rasch analysis was conducted to estimate person and item measures of the VFQ-25 and LLQ questionnaires to determine the association between the two PROs. In addition, the association between these two instruments and their correlations to weighted measures of visual function and disease progression were analyzed in this three-year PRO-focused sub-study of a fiveyear prospective natural history study.

Results: Forty-two patients participated, with most of them having completed at least two PRO follow-up visits at least one year apart. The mean VFQ-25 scores were lowest for distance activities (39.2–49.0) and peripheral vision (37.5–52.4), with mean LLQ subscale scores generally low (<41), except for the emotional distress subscale. Using Rasch analysis, calibrated item and person measures along with their standard errors were estimated for both ePROs. This indicated that the distribution of the VFQ-25 and LLQ item measures well covered the distribution of person function in this group. This suggests that the item difficulties well cover the person-level performance in this population. As well, the two PROs showed a strong and significant correlation at all assessed time points as assessed with Pearson correlation coefficient (0.81, 0.91, 0.81 and 0.87 at baseline, 1/1.5, 2/2.5 (P < 0.001) and 3/3.5 years (P = 0.002)). The composite scores of both PRO questionnaires strongly correlated with clinical measures of visual function. At 2 to 2.5 years of follow-up, meaningful statistically significant declines in peripheral vision (both VFQ-25 and LLQ), distance vision (VFQ-25), and extreme lighting in dark and bright light (LLQ) subscales were noted.

Conclusions: This study demonstrated a strong association between VFQ-25 and LLQ scores and their association with clinical measures of visual function.

Translational Relevance: PRO instruments can provide insights into the specific disabilities of this unique patient population and help to guide appropriate outcome measures for future clinical trials.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology (ARVO), 2024
Keywords
low luminance questionnaire, national eye institute visual function questionnaire, patient-reported outcomes, quality of life, retinal dystrophy, retinaldehyde-binding protein 1 (RLBP1), visual function
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:umu:diva-232486 (URN)10.1167/tvst.13.11.16 (DOI)001374746900006 ()39541109 (PubMedID)2-s2.0-85209402205 (Scopus ID)
Available from: 2024-12-10 Created: 2024-12-10 Last updated: 2025-04-24Bibliographically approved
Burstedt, M., Whelan, J. H., Green, J. S., Holopigian, K., Spera, C., Greco, E., . . . Stasi, K. (2023). Retinal dystrophy associated with RLBP1 retinitis pigmentosa: a five-year prospective natural history study. Investigative Ophthalmology and Visual Science, 64(13), Article ID 42.
Open this publication in new window or tab >>Retinal dystrophy associated with RLBP1 retinitis pigmentosa: a five-year prospective natural history study
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2023 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 64, no 13, article id 42Article in journal (Refereed) Published
Abstract [en]

Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation.

Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments.

Results: Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period.

Conclusions: This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology (ARVO), 2023
Keywords
RLBP1, retinitis pigmentosa, disease progression, dark adaptation, progressive vision loss, inherited retinal degeneration, retinal dystrophy
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-216183 (URN)10.1167/iovs.64.13.42 (DOI)001169492700007 ()37883093 (PubMedID)2-s2.0-85175357879 (Scopus ID)
Available from: 2023-11-09 Created: 2023-11-09 Last updated: 2025-04-24Bibliographically approved
Westin, I. M., Jonsson, F., Österman, L., Holmberg, M., Burstedt, M. & Golovleva, I. (2021). EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden. Scientific Reports, 11(1), Article ID 7696.
Open this publication in new window or tab >>EYS mutations and implementation of minigene assay for variant classification in EYS-associated retinitis pigmentosa in northern Sweden
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2021 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 11, no 1, article id 7696Article in journal (Refereed) Published
Abstract [en]

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations. The ortholog of Drosophila eyes shut/spacemaker, EYS on chromosome 6q12 is a major genetic cause of recessive RP worldwide, with prevalence of 5 to 30%. In this study, by using targeted NGS, MLPA and Sanger sequencing we uncovered the EYS gene as one of the most common genetic cause of autosomal recessive RP in northern Sweden accounting for at least 16%. The most frequent pathogenic variant was c.8648_8655del that in some patients was identified in cis with c.1155T>A, indicating Finnish ancestry. We also showed that two novel EYS variants, c.2992_2992+6delinsTG and c.3877+1G>A caused exon skipping in human embryonic kidney cells, HEK293T and in retinal pigment epithelium cells, ARPE-19 demonstrating that in vitro minigene assay is a straightforward tool for the analysis of intronic variants. We conclude, that whenever it is possible, functional testing is of great value for classification of intronic EYS variants and the following molecular testing of family members, their genetic counselling, and inclusion of RP patients to future treatment studies.

Place, publisher, year, edition, pages
Nature Publishing Group, 2021
National Category
Medical Genetics and Genomics Ophthalmology
Identifiers
urn:nbn:se:umu:diva-182475 (URN)10.1038/s41598-021-87224-9 (DOI)000639562100016 ()2-s2.0-85104048909 (Scopus ID)
Available from: 2021-04-29 Created: 2021-04-29 Last updated: 2025-02-10Bibliographically approved
Green, J., Tolley, C., Bentley, S., Arbuckle, R., Burstedt, M., Whelan, J., . . . Mullins, A. (2020). Qualitative Interviews to Better Understand the Patient Experience and Evaluate Patient-Reported Outcomes (PRO) in RLBP1 Retinitis Pigmentosa (RLBP1 RP). Advances in Therapy, 37(6), 2884-2901
Open this publication in new window or tab >>Qualitative Interviews to Better Understand the Patient Experience and Evaluate Patient-Reported Outcomes (PRO) in RLBP1 Retinitis Pigmentosa (RLBP1 RP)
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2020 (English)In: Advances in Therapy, ISSN 0741-238X, E-ISSN 1865-8652, Vol. 37, no 6, p. 2884-2901Article in journal (Refereed) Published
Abstract [en]

Introduction: RLBP1 RP is an autosomal recessive form of retinitis pigmentosa (RP), characterized by night blindness, prolonged dark adaptation, constricted visual fields and impaired macular function. This study aimed to better understand the patient experience of RLBP1 RP and evaluate the content validity of existing patient reported outcome (PRO) instruments in this condition.

Methods: Semi-structured concept elicitation and cognitive debriefing interviews were conducted with RLBP1 RP patients in Canada and Sweden. Interviews started with open-ended concept elicitation questioning, and then patients were cognitively debriefed on The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the Low Luminance Questionnaire (LLQ) and four light/dark adaptation items of the Visual Activities Questionnaire (VAQ). Qualitative interviews were also conducted with three expert clinicians. Anonymized, verbatim transcripts were analyzed using thematic analysis.

Results: Twenty-one patients were interviewed (Canada n = 10; Sweden n = 11). Symptoms reported included night blindness (n = 21), difficulty adapting to changes in lighting (n = 21) and difficulties seeing in bright lighting (n = 18). Patients experienced substantial impacts on daily activities (n = 21) and physical functioning (n = 17). Patients had difficulty interpreting and selecting a response for some items in the NEI VFQ-25 and LLQ. Some items were not relevant to patients’ disease experience. There were both gaps and overlaps in the conceptual coverage of the instruments.

Conclusions: Visual impairment due to RLBP1 RP has a substantial impact on physical functioning and daily activities. To adequately assess all important symptoms and associated functional impacts in RLBP1 RP, it is recommended to either modify one or more existing instruments or to develop a new non-syndromic RP specific instrument.

Place, publisher, year, edition, pages
Springer, 2020
Keywords
Interview, Qualitative, Quality of life, RLBP1 retinitis pigmentosa, RLBP1 RP, Visual functioning
National Category
Health Care Service and Management, Health Policy and Services and Health Economy
Identifiers
urn:nbn:se:umu:diva-171334 (URN)10.1007/s12325-020-01275-4 (DOI)000530588100002 ()32372289 (PubMedID)2-s2.0-85085114541 (Scopus ID)
Available from: 2020-06-11 Created: 2020-06-11 Last updated: 2023-03-23Bibliographically approved
Jonsson, F., Westin, I. M., Österman, L., Sandgren, O., Burstedt, M., Holmberg, M. & Golovleva, I. (2018). ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A > G and c.5461-10T > C cause Stargardt disease due to defective splicing. Acta Ophthalmologica, 96(7), 737-743
Open this publication in new window or tab >>ATP-binding cassette subfamily A, member 4 intronic variants c.4773+3A > G and c.5461-10T > C cause Stargardt disease due to defective splicing
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2018 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, no 7, p. 737-743Article in journal (Refereed) Published
Abstract [en]

Purpose

Inherited retinal dystrophies (IRDs) represent a group of progressive conditions affecting the retina. There is a great genetic heterogeneity causing IRDs, and to date, more than 260 genes are associated with IRDs. Stargardt disease, type 1 (STGD1) or macular degeneration with flecks, STGD1 represents a disease with early onset, central visual impairment, frequent appearance of yellowish flecks and mutations in the ATP‐binding cassette subfamily A, member 4 (ABCA4) gene. A large number of intronic sequence variants in ABCA4 have been considered pathogenic although their functional effect was seldom demonstrated. In this study, we aimed to reveal how intronic variants present in patients with Stargardt from the same Swedish family affect splicing.

Methods

The splicing of the ABCA4 gene was studied in human embryonic kidney cells, HEK293T, and in human retinal pigment epithelium cells, ARPE‐19, using a minigene system containing variants c.4773+3A>G and c.5461‐10T>C.

Results

We showed that both ABCA4 variants, c.4773+3A>G and c.5461‐10T>C, cause aberrant splicing of the ABCA4 minigene resulting in exon skipping. We also demonstrated that splicing of ABCA4 has different outcomes depending on transfected cell type.

Conclusion

Two intronic variants c.4773+3A>G and c.5461‐10T>C, both predicted to affect splicing, are indeed disease‐causing mutations due to skipping of exons 33, 34, 39 and 40 of ABCA4 gene. The experimental proof that ABCA4 mutations in STGD patients affect protein function is crucial for their inclusion to future clinical trials; therefore, functional testing of all ABCA4 intronic variants associated with Stargardt disease by minigene technology is desirable.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
ABCA4, intronic variants, mutation, splicing, Stargardt disease
National Category
Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-154068 (URN)10.1111/aos.13676 (DOI)000451035500011 ()29461686 (PubMedID)2-s2.0-85042190762 (Scopus ID)
Funder
Västerbotten County Council
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2025-02-07Bibliographically approved
Weisschuh, N., Stingl, K., Audo, I., Biskup, S., Bocquet, B., Branham, K., . . . Kohl, S. (2018). Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia. Human Mutation, 39(10), 1366-1371
Open this publication in new window or tab >>Mutations in the gene PDE6C encoding the catalytic subunit of the cone photoreceptor phosphodiesterase in patients with achromatopsia
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2018 (English)In: Human Mutation, ISSN 1059-7794, E-ISSN 1098-1004, Vol. 39, no 10, p. 1366-1371Article in journal (Refereed) Published
Abstract [en]

Biallelic PDE6C mutations are a known cause for rod monochromacy, better known as autosomal recessive achromatopsia (ACHM), and early-onset cone photoreceptor dysfunction. PDE6C encodes the catalytic alpha'-subunit of the cone photoreceptor phosphodiesterase, thereby constituting an essential part of the phototransduction cascade. Here, we present the results of a study comprising 176 genetically preselected patients who remained unsolved after Sanger sequencing of the most frequent genes accounting for ACHM, and were subsequently screened for exonic and splice site variants in PDE6C applying a targeted next generation sequencing approach. We were able to identify potentially pathogenic biallelic variants in 15 index cases. The mutation spectrum comprises 18 different alleles, 15 of which are novel. Our study significantly contributes to the mutation spectrum of PDE6C and allows for a realistic estimate of the prevalence of PDE6C mutations in ACHM since our entire ACHM cohort comprises 1,074 independent families.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
achromatopsia, cone phosphodiesterase, mutation spectrum and prevalence, PDE6C
National Category
Medical Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-152387 (URN)10.1002/humu.23606 (DOI)000444948000008 ()30080950 (PubMedID)2-s2.0-85052504166 (Scopus ID)
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2025-02-10Bibliographically approved
Jonsson, F., Burstedt, M., Kellgren, T. & Golovleva, I. (2018). Non-homologous recombination between Alu and LINE-1 repeats results in a 91 kb deletion in MERTK causing severe retinitis pigmentosa. Molecular Vision, 24, 667-678
Open this publication in new window or tab >>Non-homologous recombination between Alu and LINE-1 repeats results in a 91 kb deletion in MERTK causing severe retinitis pigmentosa
2018 (English)In: Molecular Vision, ISSN 1090-0535, Vol. 24, p. 667-678Article in journal (Refereed) Published
Abstract [en]

Purpose: Retinitis pigmentosa (RP) represents a large group of inherited retinal diseases characterized by clinical and genetic heterogeneity. Among patients with RP in northern Sweden, we identified two severely affected siblings and aimed to reveal a genetic cause underlying their disease.

Methods: Whole exome sequencing (WES) was performed on both affected individuals. Sequence variants were filtered using a custom pipeline to find a rare or novel variant predicted to affect protein function. Genome-wide genotyping was used to identify copy number variants (CNVs) and homozygous regions with potential disease causative genes.

Results: WES uncovered a novel heterozygous variant in the MER proto-oncogene, tyrosine kinase (MERTK) gene, c.2309A>G, p.Glu770Gly located in the tyrosine kinase domain and predicted to be likely pathogenic. The second variant, a large heterozygous deletion encompassing exons 1 to 7 of the MERTK gene, was revealed with genome-wide genotyping. The CNV analysis suggested breakpoints of the deletion, in the 5′-untranslated region and in intron 7. We identified genomic sequences at the site of the deletion as part of L1ME4b (LINE/L1) and AluSx3 that indicated a non-homologous recombination as a mechanism of the deletion evolvement.

Conclusions: Patients with RP in this study were carriers of two novel allelic mutations in the MERTK gene, a missense variant in exon 17 and an approximate 91 kb genomic deletion. Mapping of the deletion breakpoints allowed molecular testing of a cohort of patients with RP with allele-specific PCR. These findings provide additional information about mutations in MERTK for molecular testing of unsolved recessive RP cases and highlight the necessity for analysis of large genomic deletions.

National Category
Medical Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-153121 (URN)000447627900001 ()2-s2.0-85055736745 (Scopus ID)
Available from: 2018-11-12 Created: 2018-11-12 Last updated: 2025-02-10Bibliographically approved
Burstedt, M., Jonsson, F., Westin, I. M. & Golovleva, I. (2018). Phenotypic expression of EYS mutations in patients with autosomal recessive retinitis pigmentosa in northern Sweden. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI. Investigative Ophthalmology and Visual Science, 59(9)
Open this publication in new window or tab >>Phenotypic expression of EYS mutations in patients with autosomal recessive retinitis pigmentosa in northern Sweden
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Purpose : To describe clinical phenotype in patients of northern Sweden affected by recessive retinitis pigmentosa (ARRP) caused by mutations in Eyes Shut Homolog (Drosophila) (EYS) gene.

Methods : Whole exome sequencing (WES) and multiple ligation dependent prode amplification (MLPA) were used for identification of EYS sequence variants in a cohort of ARRP patients (n=148) from northern Sweden. The patients with EYS mutations were ophthalmologically examined over time using visual acuity (ETDRS), visual fields, slit lamp and fundus examination and ocular coherence tomography (OCT). Dark adaptometry and full-field electroretionograms (ERG) was performed.

Results : Phenotype characterization was done in 13 ARRP cases with EYS mutations representing five bi-allelic sequence variants, three of which were novel. Only one variant was detected in two cases. The phenotypic outcome was predominately presented as classical RP aggravating in young adulthood. However, among these patients we observed a variation of phenotypic expression with initial paracentral to central macular affection of the retina and areolar retinal degeneration with electrophysiological outcome of only slightly subnormal responses of both rods and cones in late adulthood (60 y/o), clinically defined as areolar atrophy.

Conclusions : The EYS mutations account for 10% of ARRP in northern Sweden. The phenotype presents both typical classical RP and chorioretinal degenerative retinal disease, areolar dystrophy. This suggests that molecular genetic testing of the EYS is crucial when both RP and pattern macular diseases are clinically diagnosed.

Place, publisher, year, edition, pages
The Association for Research in Vision and Ophthalmology, Inc., 2018
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-152275 (URN)000442912500004 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2022-06-03Bibliographically approved
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