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Byström, Berit
Publications (10 of 25) Show all publications
Boström, I. M., Viberg, A., Golovleva, I. & Byström, B. (2024). CTG18.1 expansion in transcription factor 4 (TCF4) in corneal graft failure: preliminary study. Cell and Tissue Banking, 25, 613-618
Open this publication in new window or tab >>CTG18.1 expansion in transcription factor 4 (TCF4) in corneal graft failure: preliminary study
2024 (English)In: Cell and Tissue Banking, ISSN 1389-9333, E-ISSN 1573-6814, Vol. 25, p. 613-618Article in journal (Refereed) Published
Abstract [en]

Fuchs endothelial corneal dystrophy (FECD) is caused by a corneal endothelial cell loss, leading to corneal edema and visual impairment. The most significant genetic risk factor for FECD is an expansion of the CTG18.1 locus in transcription factor 4 (TCF4). The current treatment for severe FECD is corneal transplantation, with Descemet stripping automated keratoplasty (DSAEK) as a common surgical method. Although successful in most cases, the risk for transplant failure due to diverse causes must be considered. In this study, we investigated if presence of TCF4 CTG18.1 expansion with more than 31 (n ≥ 31) repeats in donated corneal grafts could be a reason for corneal transplant failure after DSAEK. For this, nine consecutively failed DSAEK corneal grafts were genotyped for CTG18.1 repeat length. One-sided Mann–Whitney U test was performed to evaluate if failed DSAEK corneal grafts had longer CTG18.1 repeats than healthy controls from the same population. All failed corneal grafts had CTG18.1 n ≤ 27 with a median of 18 (IQR 8.0) repeats for the longest allele. There was no statistical difference in CTG18.1 repeat lengths between failed corneal grafts and the geographically matched healthy control group. In conclusion, none of the nine failed corneal grafts in our material had CTG18.1 repeat lengths ≥ 31, a cut-off known to have a biological relevance in FECD. Thus, our results suggest that the assessment of donors and inspection of the corneal tissue before the decision for procurement is sufficient, in terms of recognizing FECD in the donor.

Place, publisher, year, edition, pages
Springer Science+Business Media B.V., 2024
Keywords
CTG18.1, Descemet stripping automated keratoplasty, DSAEK, Fuchs endothelial corneal dystrophy, TCF4, Transcription factor 4
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-219760 (URN)10.1007/s10561-023-10123-y (DOI)38206443 (PubMedID)2-s2.0-85181971334 (Scopus ID)
Funder
Umeå UniversityRegion VästerbottenEye FoundationStiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadade
Available from: 2024-01-18 Created: 2024-01-18 Last updated: 2024-06-19Bibliographically approved
Viberg, A., Vicente, A., Samolov, B., Hjortdal, J. & Byström, B. (2023). Corneal transplantation in aniridia-related keratopathy with a two-year follow-up period, an uncommon disease with precarious course. Acta Ophthalmologica, 101(2), 222-228
Open this publication in new window or tab >>Corneal transplantation in aniridia-related keratopathy with a two-year follow-up period, an uncommon disease with precarious course
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2023 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 101, no 2, p. 222-228Article in journal (Refereed) Published
Abstract [en]

Purpose: The purpose of this study is to study the frequency, surgical transplantation technique and outcome in patients with aniridia-related keratopathy (ARK) with two-year follow-up period. Methods: A retrospective registry-study including all ARK cases performed in Sweden and Denmark between 2001 and 2016 and registered in the Swedish Cornea Transplant Registry. Results: A total of 36 eyes of 26 patients were subjected to corneal transplantation due to ARK during 2001 to 2016. Penetrating keratoplasty (PK) was the procedure of choice in 58.3% (n = 21) of the eyes, followed by a combination of PK and limbal stem cell transplantation in 13.9% (n = 5) and keratolimbal allograft in 13.9% (n = 5). Boston keratoprosthesis was used in 8.3% (n = 3), and anterior lamellar keratoplasty in 5.6% (n = 2). Thirteen of the procedures (36.1%) were retransplantations. Two years after surgery 26 cases were available to follow-up of which 16 of the grafts were functioning (61.5%). The median visual acuity showed a trend of improvement from hand motion to counting fingers. Conclusions: A majority of the ARK cases (61.5%) had a graft providing useful vision for the patient 2 years after corneal transplantation, but the visual gain was modest at best. Longer follow-up time is required to evaluate functional graft outcomes. Despite the introduction of limbal stem cell transplantation as a suitable treatment, PK was the most common surgical method in the present study.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
aniridia, aniridia-related keratopathy, corneal transplantation, registry-study, surgical method
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-198689 (URN)10.1111/aos.15229 (DOI)000837902300001 ()2-s2.0-85135632089 (Scopus ID)
Available from: 2022-08-19 Created: 2022-08-19 Last updated: 2023-06-20Bibliographically approved
Viberg, A., Samolov, B. & Byström, B. (2023). Descemet stripping automated endothelial keratoplasty versus descemet membrane endothelial keratoplasty for fuchs endothelial corneal dystrophy: a national registry-based comparison. Ophthalmology, 130(12), 1248-1257
Open this publication in new window or tab >>Descemet stripping automated endothelial keratoplasty versus descemet membrane endothelial keratoplasty for fuchs endothelial corneal dystrophy: a national registry-based comparison
2023 (English)In: Ophthalmology, ISSN 0161-6420, E-ISSN 1549-4713, Vol. 130, no 12, p. 1248-1257Article in journal (Refereed) Published
Abstract [en]

Purpose: To compare the outcome between posterior lamellar corneal transplant procedures for Fuchs endothelial corneal dystrophy, taking preoperative patient characteristics in consideration. Surgical methods compared were Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and DSAEK with concomitant cataract surgery (phacoemulsification plus DSAEK).

Design: Registry-based study with propensity score matching. Participants: One thousand six hundred seventy-seven patients from all Swedish corneal transplantation units treated from 2012 through 2019.

Methods: All patients undergoing endothelial keratoplasty performed from 2012 through 2019 with completed 2-year follow-up data reported to The Swedish Corneal Transplant Register were included, totaling 1677 patients. Three comparable groups (DMEK, DSAEK, and phacoemulsification plus DSAEK) with 216 patients in each group were generated with propensity score matching based on preoperative visual acuity, age, sex, year of surgery, and preoperative risk factors such as inflammation, vascularization, and glaucoma.

Main Outcome Measures: Best-corrected visual acuity (BCVA) at the 2-year follow-up, frequency of graft dislocation, graft rejection episodes, and graft failure within 2 years including primary graft failure.

Results: The preoperative corneal status was affected more severely in the DSAEK group before matching. In the matched groups, the median BCVA 2 years after surgery was 0.1 logarithm of the minimum angle of resolution (logMAR) in both the DMEK and the phacoemulsification plus DSAEK groups and 0.15 logMAR in the DSAEK group (P = 0.001). The frequency of graft dislocation was higher among the patients undergoing phacoemulsification plus DSAEK, but the frequency of graft failure and primary graft failure was higher in the DMEK group.

Conclusions: Visual acuity improved in most patients (90%) with all 3 surgical methods. However, DMEK and phacoemulsification plus DSAEK reached higher levels of visual acuity 2 years after surgery, and phacoemulsification plus DSAEK was superior considering graft survival rate. All 3 surgical procedures showed both strengths and weaknesses, suggesting that the choice of surgical method should be individualized, taking into consideration not only the cornea, but each patient's complete medical status as well as the entire course of postoperative medical care.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Cataract surgery, Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty, Fuchs endothelial corneal dystrophy, Register-based study
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-214287 (URN)10.1016/j.ophtha.2023.07.024 (DOI)37517576 (PubMedID)2-s2.0-85169845830 (Scopus ID)
Funder
Umeå UniversityRegion VästerbottenSwedish Society of MedicineStiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadade
Available from: 2023-09-11 Created: 2023-09-11 Last updated: 2023-12-20Bibliographically approved
Westin, I. M., Landfors, M., Giannopoulos, A., Viberg, A., Osterman, P., Byström, B., . . . Golovleva, I. (2023). DNA methylation changes and increased mRNA expression of coagulation proteins, factor V and thrombomodulin in Fuchs endothelial corneal dystrophy. Cellular and Molecular Life Sciences (CMLS), 80(3), Article ID 62.
Open this publication in new window or tab >>DNA methylation changes and increased mRNA expression of coagulation proteins, factor V and thrombomodulin in Fuchs endothelial corneal dystrophy
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2023 (English)In: Cellular and Molecular Life Sciences (CMLS), ISSN 1420-682X, E-ISSN 1420-9071, Vol. 80, no 3, article id 62Article in journal (Refereed) Published
Abstract [en]

Late-onset Fuchs endothelial corneal dystrophy (FECD) is a disease affecting the corneal endothelium (CE), associated with a cytosine-thymine-guanine repeat expansion at the CTG18.1 locus in the transcription factor 4 (TCF4) gene. It is unknown whether CTG18.1 expansions affect global methylation including TCF4 gene in CE or whether global CE methylation changes at advanced age. Using genome-wide DNA methylation array, we investigated methylation in CE from FECD patients with CTG18.1 expansions and studied the methylation in healthy CE at different ages. The most revealing DNA methylation findings were analyzed by gene expression and protein analysis. 3488 CpGs had significantly altered methylation pattern in FECD though no substantial changes were found in TCF4. The most hypermethylated site was in a predicted promoter of aquaporin 1 (AQP1) gene, and the most hypomethylated site was in a predicted promoter of coagulation factor V (F5 for gene, FV for protein). In FECD, AQP1 mRNA expression was variable, while F5 gene expression showed a ~ 23-fold increase. FV protein was present in both healthy and affected CE. Further gene expression analysis of coagulation factors interacting with FV revealed a ~ 34-fold increase of thrombomodulin (THBD). THBD protein was detected only in CE from FECD patients. Additionally, we observed an age-dependent hypomethylation in elderly healthy CE.Thus, tissue-specific genome-wide and gene-specific methylation changes associated with altered gene expression were discovered in FECD. TCF4 pathological methylation in FECD because of CTG18.1 expansion was ruled out.

Place, publisher, year, edition, pages
Springer, 2023
Keywords
Coagulation factors; DNA methylation; Factor V; Fuchs dystrophy; Thrombomodulin; Transcription factor 4 (TCF4); Trinucleotide repeat disorder
National Category
Medical Genetics
Research subject
Medical Genetics; Medical Genetics
Identifiers
urn:nbn:se:umu:diva-200178 (URN)10.21203/rs.3.rs-1758860/v1 (DOI)000929515100001 ()36773096 (PubMedID)2-s2.0-85147894855 (Scopus ID)
Funder
Region VästerbottenUmeå UniversityStiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadadeThe Kempe Foundations
Note

Originally included in thesis in manuscript form. 

Available from: 2022-10-12 Created: 2022-10-12 Last updated: 2023-09-05Bibliographically approved
Vicente, A., Sloniecka, M., Liu, J.-X., Byström, B. & Domellöf, F. P. (2022). Aniridia-related keratopathy relevant cell signaling pathways in human fetal corneas. Histochemistry and Cell Biology, 158(2), 169-180
Open this publication in new window or tab >>Aniridia-related keratopathy relevant cell signaling pathways in human fetal corneas
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2022 (English)In: Histochemistry and Cell Biology, ISSN 0948-6143, E-ISSN 1432-119X, Vol. 158, no 2, p. 169-180Article in journal (Refereed) Published
Abstract [en]

We aimed to study aniridia-related keratopathy (ARK) relevant cell signaling pathways [Notch1, Wnt/β-catenin, Sonic hedgehog (SHH) and mTOR] in normal human fetal corneas compared with normal human adult corneas and ARK corneas. We found that fetal corneas at 20 weeks of gestation (wg) and normal adult corneas showed similar staining patterns for Notch1; however 10–11 wg fetal corneas showed increased presence of Notch1. Numb and Dlk1 had an enhanced presence in the fetal corneas compared with the adult corneas. Fetal corneas showed stronger immunolabeling with antibodies against β-catenin, Wnt5a, Wnt7a, Gli1, Hes1, p-rpS6, and mTOR when compared with the adult corneas. Gene expression of Notch1, Wnt5A, Wnt7A, β-catenin, Hes1, mTOR, and rps6 was higher in the 9–12 wg fetal corneas compared with adult corneas. The cell signaling pathway differences found between human fetal and adult corneas were similar to those previously found in ARK corneas with the exception of Notch1. Analogous profiles of cell signaling pathway activation between human fetal corneas and ARK corneas suggests that there is a less differentiated host milieu in ARK.

Place, publisher, year, edition, pages
Springer, 2022
Keywords
Aniridia, Fetal cornea, Adult cornea, Sonic hedgehog, Notch, mTOR, Wnt
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-164256 (URN)10.1007/s00418-022-02099-9 (DOI)000799082100002 ()35551459 (PubMedID)2-s2.0-85129792626 (Scopus ID)
Funder
Region VästerbottenUmeå UniversityStiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadadeÅke Wiberg Foundation
Note

Originally included in thesis in manuscript form.

Available from: 2019-10-18 Created: 2019-10-18 Last updated: 2023-09-05Bibliographically approved
Viberg, A., Westin, I. M., Golovleva, I. & Byström, B. (2022). TCF4 trinucleotide repeat expansion in Swedish cases with Fuchs’ endothelial corneal dystrophy. Acta Ophthalmologica, 100(5), 541-548
Open this publication in new window or tab >>TCF4 trinucleotide repeat expansion in Swedish cases with Fuchs’ endothelial corneal dystrophy
2022 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 100, no 5, p. 65p. 541-548Article in journal (Refereed) Published
Abstract [en]

Purpose: Fuchs' endothelial corneal dystrophy (FECD) has been considered a genetically heterogeneous disease but is increasingly associated with the transcription factor 4 (TCF4) gene. This study investigates the prevalence of the cytosine-thymine-guanine (CTG)n repeat expansion in TCF4 among FECD patients in northern Sweden coupled to the phenotype.

Methods: Blood samples were collected from 85 FECD cases at different stages. Short tandem repeat PCR and triplet repeat-primed PCR were applied in order to determine TCF4 (CTG)n genotype.

Results: A (CTG)n repeat expansion (n > 50) in TCF4 was identified in 76 of 85 FECD cases (89.4%) and in four of 102 controls (3.9%). The median (CTG)n repeat length was 81 (IQR 39.3) in mild FECD and 87 (IQR 13.0) in severe FECD (p = 0.01). A higher number of (CTG)n repeats in an expanded TCF4 allele increased the probability of severe FECD. Other ocular surgery was overrepresented in FECD cases without a (CTG)n repeat expansion (44.4%, n = 4) compared with 3.9% (n = 3) in FECD cases with an (CTG)n repeat expansion (p < 0.001).

Conclusion: In northern Sweden, the FECD phenotype is associated with (CTG)n expansion in the TCF4 gene, with nearly 90% of patients being hetero- or homozygous for (CTG)n expansion over 50 repeats. Furthermore, the severity of FECD was associated with the repeat length in the TCF4 gene. Ocular surgery might act as an environmental factor explaining the clinical disease in FECD without a repeat expansion in TCF4.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022. p. 65
Keywords
cornea, Fuchs’ endothelial corneal dystrophy, genetic aetiology, TCF4, trinucleotide repeat disorders
National Category
Ophthalmology
Research subject
ophthalmology; Medical Genetics
Identifiers
urn:nbn:se:umu:diva-187710 (URN)10.1111/aos.15032 (DOI)000706786900001 ()34644448 (PubMedID)2-s2.0-85116925455 (Scopus ID)978-91-7855-588-8 (ISBN)978-91-7855-589-5 (ISBN)
Funder
Stiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadadeRegion Västerbotten
Note

Previously included in thesis in manuscript form.

Available from: 2021-09-18 Created: 2021-09-18 Last updated: 2022-11-29Bibliographically approved
Viberg, A. & Byström, B. (2021). Incidence of corneal transplantation after challenging cataract surgery in patients with and without corneal guttata. Journal of cataract and refractive surgery, 47(3), 358-365
Open this publication in new window or tab >>Incidence of corneal transplantation after challenging cataract surgery in patients with and without corneal guttata
2021 (English)In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 47, no 3, p. 358-365Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To study the risk for corneal transplantation after phacoemulsification with dense cataract or posterior capsule rupture (PCR) and the impact of corneal guttata.

SETTING: Forty-nine Swedish cataract surgical units and 8 Swedish cornea transplantation units.

DESIGN: Registry-based cohort study.

METHODS: Patient data from the Swedish National Cataract Registry (2010 to 2012) were linked with data from the Swedish Cornea Transplant Registry (2010 to 2017). The outcome measures were risk for future corneal transplantation, visual acuity, and self-assessed visual function after phacoemulsification. Logistic and Poisson regression analyses with adjustment for confounder effects were used to investigate the association of the outcome measures with dense cataract, indicated by trypan blue capsular staining (TB) and PCR, separately and together.

RESULTS: Altogether, data from 276 362 cataract patients were linked with data from 2091 patients with endothelial failure who underwent corneal transplantation.The risk for future corneal transplantation increased more than 3-fold with the presence of dense cataract or PCR, and a trend toward an ever-higher risk with the combination of TB and PCR together, but without any significant synergy of corneal guttata. Dense cataract, but not PCR, was significantly associated with an increased probability of inferior visual acuity after phacoemulsification. The impact on satisfaction was not statistically significant for any of the factors.

CONCLUSIONS: Challenging cataract surgery increases the risk for future corneal transplantation equally in patients both with and without corneal guttata, despite a more vulnerable endothelium in the guttata group. This supports a strategy where PCR is limited and handled optimally and that cataract surgery is performed before the cataract turns critically dense.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2021
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-183636 (URN)10.1097/j.jcrs.0000000000000451 (DOI)000624944300013 ()33086292 (PubMedID)2-s2.0-85105762852 (Scopus ID)
Available from: 2021-05-27 Created: 2021-05-27 Last updated: 2021-09-22Bibliographically approved
Westin, I. M., Viberg, A., Byström, B. & Golovleva, I. (2021). Lower fractions of TCF4 transcripts spanning over the CTG18.1 trinucleotide repeat in human corneal endothelium. Genes, 12(12), Article ID 2006.
Open this publication in new window or tab >>Lower fractions of TCF4 transcripts spanning over the CTG18.1 trinucleotide repeat in human corneal endothelium
2021 (English)In: Genes, E-ISSN 2073-4425, Vol. 12, no 12, article id 2006Article in journal (Refereed) Published
Abstract [en]

Fuchs’ endothelial corneal dystrophy (FECD) is a bilateral disease of the cornea caused by gradual loss of corneal endothelial cells. Late-onset FECD is strongly associated with the CTG18.1 trinucleotide repeat expansion in the Transcription Factor 4 gene (TCF4), which forms RNA nuclear foci in corneal endothelial cells. To date, 46 RefSeq transcripts of TCF4 are annotated by the National Center of Biotechnology information (NCBI), however the effect of the CTG18.1 expansion on expression of alternative TCF4 transcripts is not completely understood. To investigate this, we used droplet digital PCR for quantification of TCF4 transcripts spanning over the CTG18.1 and transcripts with transcription start sites immediately downstream of the CTG18.1. TCF4 expression was analysed in corneal endothelium and in whole blood of FECD patients with and without CTG18.1 expansion, in non-FECD controls without CTG18.1 expansion, and in five additional control tissues. Subtle changes in transcription levels in groups of TCF4 transcripts were detected. In corneal endothelium, we found a lower fraction of transcripts spanning over the CTG18.1 tract compared to all other tissues investigated.

Place, publisher, year, edition, pages
MDPI, 2021
Keywords
Alternative transcripts, DdPCR, Fuchs corneal dystrophy, MRNA expression, Transcription Factor 4 (TCF4)
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-190871 (URN)10.3390/genes12122006 (DOI)000737561800001 ()2-s2.0-85121416878 (Scopus ID)
Funder
Region VästerbottenStiftelsen Kronprinsessan Margaretas arbetsnämnd för synskadade
Available from: 2021-12-30 Created: 2021-12-30 Last updated: 2024-07-04Bibliographically approved
Viberg, A., Samolov, B., Claesson Armitage, M., Behndig, A. & Byström, B. (2020). Incidence of corneal transplantation after phacoemulsification in patients with corneal guttata: a registry-based cohort study. Paper presented at 22nd Conference of the European-Association-for-Vision-and-Eye-Research (EVER), OCT 17-19, 2019, Nice, FRANCE. Journal of cataract and refractive surgery, 46(7), 961-966
Open this publication in new window or tab >>Incidence of corneal transplantation after phacoemulsification in patients with corneal guttata: a registry-based cohort study
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2020 (English)In: Journal of cataract and refractive surgery, ISSN 0886-3350, E-ISSN 1873-4502, Vol. 46, no 7, p. 961-966Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the risk for corneal transplantation after phacoemulsification related to corneal guttata.

Setting: Forty-nine Swedish cataract surgical units and 7 Swedish cornea transplantation units.

Design: Registry-based cohort study.

Methods: Patient data from the Swedish National Cataract Registry between 2010 and 2012 were linked with data from the Swedish Cornea Transplant Registry between 2010 and September 2017. Data from cataract patients were linked with data from patients who underwent corneal transplantation because of endothelial failure. Triple procedures and other surgical methods for cataract extraction other than phacoemulsification were excluded. If both eyes had surgery, 1 eye was randomly selected from the registry to obtain unrelated samples. The incidence was calculated per 10 000 person years, and Poisson regression analysis was used to investigate the risk for corneal transplantation because of endothelial failure after phacoemulsification.

Results: Altogether, data from 276 362 cataract patients were linked with data from 2091 patients who underwent corneal transplantation. The incidence rate of corneal transplantation after phacoemulsification among patients with corneal guttata was 88 per 10 000 person years (95% CI, 74.5-103.1). The annual incidence rate was highest within the first year and diminished thereafter. The incidence rate of corneal transplantation among patients without corneal guttata was 1.4 per 10 000 person years (95% CI, 1.2-1.6). Phacoemulsification in patients with corneal guttata was associated with corneal transplantation with an adjusted relative risk of 68.2 (95% CI, 54.0-86.2).

Conclusions: The relative risk for corneal transplantation after phacoemulsification was 68.2 times higher for patients with corneal guttata than that for those without. Still, most of the patients with corneal guttata did not undergo corneal transplantation during the study period.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2020
National Category
Surgery Ophthalmology
Identifiers
urn:nbn:se:umu:diva-176463 (URN)10.1097/j.jcrs.0000000000000207 (DOI)000579542200006 ()32271268 (PubMedID)2-s2.0-85089358901 (Scopus ID)
Conference
22nd Conference of the European-Association-for-Vision-and-Eye-Research (EVER), OCT 17-19, 2019, Nice, FRANCE
Available from: 2020-11-19 Created: 2020-11-19 Last updated: 2021-09-22Bibliographically approved
Byström, B. (2019). Corneal recurrent erosions dystrophies in Sweden. Acta Ophthalmologica, 97(S263)
Open this publication in new window or tab >>Corneal recurrent erosions dystrophies in Sweden
2019 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 97, no S263Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Corneal dystrophies are a heterogeneous group of genetic disorders. We aimed to identify genetic cause of a dominantly inherited Epithelial Recurrent Erosion Dystrophy (ERED )‐like disease common in Northern Sweden. Examinations and interviews were performed at the Ophthalmology Clinics of the University Hospital of Umeå and Skellefteå Hospital. A total of 20 patients from Västerbotten were extensively examined and blood samples for genetic analysis collected. Four unrelated families were subject to genealogical studies. Known genes causative of corneal dystrophies were excluded by array‐based allele specific primer extension. Haplotype assessment was done by array genotyping and identification of potentially causative genomic variants by whole exome sequencing (WES ). The dystrophy common in Västerbotten has three phases; recurrent erosions during childhood, alleviated symptoms in the higher teens and finally, after the age 40, decreased visual acuity. Haplotype analysis and WES revealed a novel mutation, c.2816C>T, p.T939I, in the COL 17A1 gene coding collagen type XVII alpha1. It appeared to be a founder mutation that segregated with disease in a genealogically expanded pedigree dating back 200 years to a common ancestor, Theodor. Notably, the patients called the disease ‘Theodor's eyes’, but Theodor being unknown to them. Furthermore, COL 17A1 expression in cornea was demonstrated by RT ‐PCR and immunohistochemistry. We identified COL 17A1 mutation as a cause of ERED , revealing a novel corneal disease in Sweden, and highlighting the necessity of COL 17A1 screening in corneal dystrophies with erosions and no known genetic defect. Our genealogical analysis identified a common ancestor, Theodor, living 200 years ago.

Place, publisher, year, edition, pages
John Wiley & Sons, 2019
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-173874 (URN)10.1111/j.1755-3768.2019.8264 (DOI)000540559500377 ()
Available from: 2020-08-06 Created: 2020-08-06 Last updated: 2020-08-06Bibliographically approved
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