The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene

Daniel C Chung; Mette Bertelsen; Birgit Lorenz; Mark E Pennesi; Bart P Leroy; Christian P Hamel; Eric Pierce; Juliana Sallum; Michael Larsen; Knut Stieger; Markus Preising; Richard Weleber; Paul Yang; Emily Place; Emily Liu; Grace Schaefer; Julie DiStefano-Pappas; Okan U Elci; Sarah McCague; Jennifer A Wellman; Katherine A High; Kathleen Z Reape

doi:10.1016/j.ajo.2018.09.024

The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene

Daniel C Chung, Mette Bertelsen, Birgit Lorenz, Mark E Pennesi, Bart P Leroy, Christian P Hamel, Eric Pierce, Juliana Sallum, Michael Larsen, Knut Stieger, Markus Preising, Richard Weleber, Paul Yang, Emily Place, Emily Liu, Grace Schaefer, Julie DiStefano-Pappas, Okan U Elci, Sarah McCague, Jennifer A WellmanKatherine A High, Kathleen Z Reape

Developmental biology - endoderm and pancreas development

19 Citationer (Scopus)

Abstract

Purpose: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation–associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. Design: Global, multicenter, retrospective chart review. Methods: STUDY POPULATION: Seventy individuals with biallelic RPE65 mutation–associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). Results: VA decreased with age in a nonlinear, positive-acceleration relationship (P <.001). GVF decreased with age (P <.0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P =.0114, left eye; P =.0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. Conclusions: The number of clinical diagnoses and lack of a consistent RPE65 mutation–to–phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.

Originalsprog	Engelsk
Tidsskrift	American Journal of Ophthalmology
Vol/bind	199
Sider (fra-til)	58-70
Antal sider	13
ISSN	0002-9394
DOI	https://doi.org/10.1016/j.ajo.2018.09.024
Status	Udgivet - mar. 2019

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10.1016/j.ajo.2018.09.024

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Chung, D. C., Bertelsen, M., Lorenz, B., Pennesi, M. E., Leroy, B. P., Hamel, C. P., Pierce, E., Sallum, J., Larsen, M., Stieger, K., Preising, M., Weleber, R., Yang, P., Place, E., Liu, E., Schaefer, G., DiStefano-Pappas, J., Elci, O. U., McCague, S., ... Reape, K. Z. (2019). The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene. American Journal of Ophthalmology, 199, 58-70. https://doi.org/10.1016/j.ajo.2018.09.024

Chung, DC, Bertelsen, M, Lorenz, B, Pennesi, ME, Leroy, BP, Hamel, CP, Pierce, E, Sallum, J, Larsen, M, Stieger, K, Preising, M, Weleber, R, Yang, P, Place, E, Liu, E, Schaefer, G, DiStefano-Pappas, J, Elci, OU, McCague, S, Wellman, JA, High, KA & Reape, KZ 2019, 'The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene', American Journal of Ophthalmology, bind 199, s. 58-70. https://doi.org/10.1016/j.ajo.2018.09.024

@article{a3e71e00888d4ce8bc0eb6634b1d44f5,

title = "The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene",

abstract = "Purpose: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation–associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. Design: Global, multicenter, retrospective chart review. Methods: STUDY POPULATION: Seventy individuals with biallelic RPE65 mutation–associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). Results: VA decreased with age in a nonlinear, positive-acceleration relationship (P <.001). GVF decreased with age (P <.0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P =.0114, left eye; P =.0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. Conclusions: The number of clinical diagnoses and lack of a consistent RPE65 mutation–to–phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.",

author = "Chung, {Daniel C} and Mette Bertelsen and Birgit Lorenz and Pennesi, {Mark E} and Leroy, {Bart P} and Hamel, {Christian P} and Eric Pierce and Juliana Sallum and Michael Larsen and Knut Stieger and Markus Preising and Richard Weleber and Paul Yang and Emily Place and Emily Liu and Grace Schaefer and Julie DiStefano-Pappas and Elci, {Okan U} and Sarah McCague and Wellman, {Jennifer A} and High, {Katherine A} and Reape, {Kathleen Z}",

year = "2019",

month = mar,

doi = "10.1016/j.ajo.2018.09.024",

language = "English",

volume = "199",

pages = "58--70",

journal = "American Journal of Ophthalmology",

issn = "0002-9394",

publisher = "Elsevier",

}

TY - JOUR

T1 - The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene

AU - Chung, Daniel C

AU - Bertelsen, Mette

AU - Lorenz, Birgit

AU - Pennesi, Mark E

AU - Leroy, Bart P

AU - Hamel, Christian P

AU - Pierce, Eric

AU - Sallum, Juliana

AU - Larsen, Michael

AU - Stieger, Knut

AU - Preising, Markus

AU - Weleber, Richard

AU - Yang, Paul

AU - Place, Emily

AU - Liu, Emily

AU - Schaefer, Grace

AU - DiStefano-Pappas, Julie

AU - Elci, Okan U

AU - McCague, Sarah

AU - Wellman, Jennifer A

AU - High, Katherine A

AU - Reape, Kathleen Z

PY - 2019/3

Y1 - 2019/3

N2 - Purpose: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation–associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. Design: Global, multicenter, retrospective chart review. Methods: STUDY POPULATION: Seventy individuals with biallelic RPE65 mutation–associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). Results: VA decreased with age in a nonlinear, positive-acceleration relationship (P <.001). GVF decreased with age (P <.0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P =.0114, left eye; P =.0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. Conclusions: The number of clinical diagnoses and lack of a consistent RPE65 mutation–to–phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.

AB - Purpose: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation–associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. Design: Global, multicenter, retrospective chart review. Methods: STUDY POPULATION: Seventy individuals with biallelic RPE65 mutation–associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). Results: VA decreased with age in a nonlinear, positive-acceleration relationship (P <.001). GVF decreased with age (P <.0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P =.0114, left eye; P =.0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. Conclusions: The number of clinical diagnoses and lack of a consistent RPE65 mutation–to–phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.

U2 - 10.1016/j.ajo.2018.09.024

DO - 10.1016/j.ajo.2018.09.024

M3 - Journal article

C2 - 30268864

SN - 0002-9394

VL - 199

SP - 58

EP - 70

JO - American Journal of Ophthalmology

JF - American Journal of Ophthalmology

ER -

The Natural History of Inherited Retinal Dystrophy Due to Biallelic Mutations in the RPE65 Gene

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