Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290

Dyon Valkenburg; Caroline van Cauwenbergh; Birgit Lorenz; Mies M van Genderen; Mette Bertelsen; Jan-Willem R Pott; Frauke Coppieters; Julie de Zaeytijd; Alberta A H J Thiadens; Caroline C W Klaver; Hester Y Kroes; Mary J van Schooneveld; Markus Preising; Carel B Hoyng; Bart P Leroy; L Ingeborgh van den Born; Rob W J Collin

doi:10.1167/iovs.18-24817

Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290

Dyon Valkenburg, Caroline van Cauwenbergh, Birgit Lorenz, Mies M van Genderen, Mette Bertelsen, Jan-Willem R Pott, Frauke Coppieters, Julie de Zaeytijd, Alberta A H J Thiadens, Caroline C W Klaver, Hester Y Kroes, Mary J van Schooneveld, Markus Preising, Carel B Hoyng, Bart P Leroy, L Ingeborgh van den Born, Rob W J Collin

Medical retina and Uveitis

Research output: Contribution to journal › Article › Research › peer-review

Abstract

Purpose: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients.

Methods: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence was assessed using spectral-domain optical coherence tomography (SD-OCT). Differences between compound heterozygous and homozygous patients were analyzed based on visual performance and visual development.

Results: A total of 66 patients were included. The majority of patients had either light perception or no light perception. In the remaining group of 14 patients, median BCVA was 20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148 Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended to be more likely to develop light perception compared to more severely affected compound heterozygous patients (P = 0.080) and are more likely to improve from no light perception to light perception (P = 0.022) before the age of 6 years. OCT data were available in 12 patients, 11 of whom had retained foveal ONL and EZ integrity up to 48 years (median 23 years) of age.

Conclusions: Homozygous patients seem less severely affected compared to their compound-heterozygous peers. Improvement of visual function may occur in the early years of life, suggesting a time window for therapeutic intervention up to the approximate age of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT.

Original language	English
Pages (from-to)	4384-4391
Number of pages	8
Journal	Investigative ophthalmology & visual science
Volume	59
Issue number	11
DOIs	https://doi.org/10.1167/iovs.18-24817
Publication status	Published - 4 Sept 2018

Keywords

Adolescent
Adult
Antigens, Neoplasm/genetics
Child
Child, Preschool
Electroretinography
Female
Follow-Up Studies
Gene Amplification
High-Throughput Nucleotide Sequencing
Humans
Infant
Introns/genetics
Leber Congenital Amaurosis/diagnosis
Male
Middle Aged
Mutation
Neoplasm Proteins/genetics
Polymerase Chain Reaction
Retina/diagnostic imaging
Retrospective Studies
Tomography, Optical Coherence
Visual Acuity/physiology
Young Adult

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10.1167/iovs.18-24817

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Valkenburg, D., van Cauwenbergh, C., Lorenz, B., van Genderen, M. M., Bertelsen, M., Pott, J.-W. R., Coppieters, F., de Zaeytijd, J., Thiadens, A. A. H. J., Klaver, C. C. W., Kroes, H. Y., van Schooneveld, M. J., Preising, M., Hoyng, C. B., Leroy, B. P., van den Born, L. I., & Collin, R. W. J. (2018). Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290. Investigative ophthalmology & visual science, 59(11), 4384-4391. https://doi.org/10.1167/iovs.18-24817

@article{7109b09a3bf5470a84fec45da39b1579,

title = "Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290",

abstract = "Purpose: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients.Methods: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence was assessed using spectral-domain optical coherence tomography (SD-OCT). Differences between compound heterozygous and homozygous patients were analyzed based on visual performance and visual development.Results: A total of 66 patients were included. The majority of patients had either light perception or no light perception. In the remaining group of 14 patients, median BCVA was 20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148 Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended to be more likely to develop light perception compared to more severely affected compound heterozygous patients (P = 0.080) and are more likely to improve from no light perception to light perception (P = 0.022) before the age of 6 years. OCT data were available in 12 patients, 11 of whom had retained foveal ONL and EZ integrity up to 48 years (median 23 years) of age.Conclusions: Homozygous patients seem less severely affected compared to their compound-heterozygous peers. Improvement of visual function may occur in the early years of life, suggesting a time window for therapeutic intervention up to the approximate age of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT.",

keywords = "Adolescent, Adult, Antigens, Neoplasm/genetics, Child, Child, Preschool, Electroretinography, Female, Follow-Up Studies, Gene Amplification, High-Throughput Nucleotide Sequencing, Humans, Infant, Introns/genetics, Leber Congenital Amaurosis/diagnosis, Male, Middle Aged, Mutation, Neoplasm Proteins/genetics, Polymerase Chain Reaction, Retina/diagnostic imaging, Retrospective Studies, Tomography, Optical Coherence, Visual Acuity/physiology, Young Adult",

author = "Dyon Valkenburg and {van Cauwenbergh}, Caroline and Birgit Lorenz and {van Genderen}, {Mies M} and Mette Bertelsen and Pott, {Jan-Willem R} and Frauke Coppieters and {de Zaeytijd}, Julie and Thiadens, {Alberta A H J} and Klaver, {Caroline C W} and Kroes, {Hester Y} and {van Schooneveld}, {Mary J} and Markus Preising and Hoyng, {Carel B} and Leroy, {Bart P} and {van den Born}, {L Ingeborgh} and Collin, {Rob W J}",

year = "2018",

month = sep,

day = "4",

doi = "10.1167/iovs.18-24817",

language = "English",

volume = "59",

pages = "4384--4391",

number = "11",

}

Valkenburg, D, van Cauwenbergh, C, Lorenz, B, van Genderen, MM, Bertelsen, M, Pott, J-WR, Coppieters, F, de Zaeytijd, J, Thiadens, AAHJ, Klaver, CCW, Kroes, HY, van Schooneveld, MJ, Preising, M, Hoyng, CB, Leroy, BP, van den Born, LI & Collin, RWJ 2018, 'Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290', Investigative ophthalmology & visual science, vol. 59, no. 11, pp. 4384-4391. https://doi.org/10.1167/iovs.18-24817

Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290. / Valkenburg, Dyon; van Cauwenbergh, Caroline; Lorenz, Birgit et al.
In: Investigative ophthalmology & visual science, Vol. 59, No. 11, 04.09.2018, p. 4384-4391.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290

AU - Valkenburg, Dyon

AU - van Cauwenbergh, Caroline

AU - Lorenz, Birgit

AU - van Genderen, Mies M

AU - Bertelsen, Mette

AU - Pott, Jan-Willem R

AU - Coppieters, Frauke

AU - de Zaeytijd, Julie

AU - Thiadens, Alberta A H J

AU - Klaver, Caroline C W

AU - Kroes, Hester Y

AU - van Schooneveld, Mary J

AU - Preising, Markus

AU - Hoyng, Carel B

AU - Leroy, Bart P

AU - van den Born, L Ingeborgh

AU - Collin, Rob W J

PY - 2018/9/4

Y1 - 2018/9/4

N2 - Purpose: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients.Methods: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence was assessed using spectral-domain optical coherence tomography (SD-OCT). Differences between compound heterozygous and homozygous patients were analyzed based on visual performance and visual development.Results: A total of 66 patients were included. The majority of patients had either light perception or no light perception. In the remaining group of 14 patients, median BCVA was 20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148 Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended to be more likely to develop light perception compared to more severely affected compound heterozygous patients (P = 0.080) and are more likely to improve from no light perception to light perception (P = 0.022) before the age of 6 years. OCT data were available in 12 patients, 11 of whom had retained foveal ONL and EZ integrity up to 48 years (median 23 years) of age.Conclusions: Homozygous patients seem less severely affected compared to their compound-heterozygous peers. Improvement of visual function may occur in the early years of life, suggesting a time window for therapeutic intervention up to the approximate age of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT.

AB - Purpose: To describe the phenotypic spectrum of retinal disease caused by the c.2991+1655A>G mutation in CEP290 and to compare disease severity between homozygous and compound heterozygous patients.Methods: Medical records were reviewed for best-corrected visual acuity (BCVA), age of onset, fundoscopy descriptions. Foveal outer nuclear layer (ONL) and ellipsoid zone (EZ) presence was assessed using spectral-domain optical coherence tomography (SD-OCT). Differences between compound heterozygous and homozygous patients were analyzed based on visual performance and visual development.Results: A total of 66 patients were included. The majority of patients had either light perception or no light perception. In the remaining group of 14 patients, median BCVA was 20/195 Snellen (0.99 LogMAR; range 0.12-1.90) for the right eye, and 20/148 Snellen (0.87 LogMAR; range 0.22-1.90) for the left. Homozygous patients tended to be more likely to develop light perception compared to more severely affected compound heterozygous patients (P = 0.080) and are more likely to improve from no light perception to light perception (P = 0.022) before the age of 6 years. OCT data were available in 12 patients, 11 of whom had retained foveal ONL and EZ integrity up to 48 years (median 23 years) of age.Conclusions: Homozygous patients seem less severely affected compared to their compound-heterozygous peers. Improvement of visual function may occur in the early years of life, suggesting a time window for therapeutic intervention up to the approximate age of 17 years. This period may be extended by an intact foveal ONL and EZ on OCT.

KW - Adolescent

KW - Adult

KW - Antigens, Neoplasm/genetics

KW - Child

KW - Child, Preschool

KW - Electroretinography

KW - Female

KW - Follow-Up Studies

KW - Gene Amplification

KW - High-Throughput Nucleotide Sequencing

KW - Humans

KW - Infant

KW - Introns/genetics

KW - Leber Congenital Amaurosis/diagnosis

KW - Male

KW - Middle Aged

KW - Mutation

KW - Neoplasm Proteins/genetics

KW - Polymerase Chain Reaction

KW - Retina/diagnostic imaging

KW - Retrospective Studies

KW - Tomography, Optical Coherence

KW - Visual Acuity/physiology

KW - Young Adult

U2 - 10.1167/iovs.18-24817

DO - 10.1167/iovs.18-24817

M3 - Article

C2 - 30193310

SN - 0146-0404

VL - 59

SP - 4384

EP - 4391

JO - Investigative ophthalmology & visual science

JF - Investigative ophthalmology & visual science

IS - 11

ER -

Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290

Abstract

Keywords

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