Abstract
Introduction: The purpose of this study was to compare clinical/demographic functional testing and multimodal imaging features between genetically solved and genetically unsolved nonsyndromic retinitis pigmentosa (nsRP) patients. Methods: A cross-sectional study was conducted at an inherited retinal dystrophies reference center. Consecutive patients with nsRP and available genetic testing results performed between 2018 and 2020 were included. Genetic testing was clinically oriented, and variants were classified according to the American College of Medical Genetics and Genomics. Only class IV or V variants were considered disease-causing. Clinical/demographic, functional, and imaging features were compared between genetically unsolved (G1) and genetically solved (G2) patients. Results: A total of 175 patients (146 families) were included: 68 patients (59 families) in G1 and 107 patients (87 families) in G2. First symptoms <25 years, consanguinity, evidence for a particular inheritance pattern, and the absence of indicators for phenocopies were significantly more prevalent in G2. No significant differences were observed on best-corrected visual acuity. The visual field index and mean central retinal layer thickness were significantly higher in G1. The frequency of atypical features on multimodal imaging did not differ between groups. Conclusion: Individual clinical/demographic functional testing and multimodal imaging features should be considered when counseling patients about the probability of identifying disease-causing variants.
References
1.
Verbakel
SK
, van Huet
RAC
, Boon
CJF
, den Hollander
AI
, Collin
RWJ
, Klaver
CCW
, Non-syndromic retinitis pigmentosa
. Prog Retin Eye Res
. 2018
;66
:157
–86
. .2.
Schuerch
K
, Marsiglia
M
, Lee
W
, Tsang
SH
, Sparrow
JR
. Multimodal imaging of disease-associated pigmentary changes in retinitis pigmentosa
. Retina
. 2016
;36
(Suppl 1
):S147
–S58
. .3.
Sujirakul
T
, Davis
R
, Erol
D
, Zhang
L
, Schillizzi
G
, Royo-Dujardin
L
, Bilateral concordance of the fundus hyperautofluorescent ring in typical retinitis pigmentosa patients
. Ophthalmic Genet
. 2015
;36
(2
):113
–22
. .4.
Farrell
DF
. Unilateral retinitis pigmentosa and cone-rod dystrophy
. Clin Ophthalmol
. 2009
;3
:263
–70
. .5.
Jauregui
R
, Chan
L
, Oh
JK
, Cho
A
, Sparrow
JR
, Tsang
SH
. Disease asymmetry and hyperautofluorescent ring shape in retinitis pigmentosa patients
. Sci Rep
. 2020
;10
(1
):3364
. .6.
Gao
FJ
, Li
JK
, Chen
H
, Hu
FY
, Zhang
SH
, Qi
YH
, Genetic and clinical findings in a large cohort of chinese patients with suspected retinitis pigmentosa
. Ophthalmology
. 2019
;126
(11
):1549
–56
. .7.
Perea-Romero
I
, Gordo
G
, Iancu
IF
, Pozo-Valero
MD
, Almoguera
B
, Blanco-Kelly
F
, Genetic landscape of 6,089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications
. Sci Rep
. 2021
;11
(1
):1526
.8.
Birtel
J
, Gliem
M
, Mangold
E
, Müller
PL
, Holz
FG
, Neuhaus
C
, Next-generation sequencing identifies unexpected genotype-phenotype correlations in patients with retinitis pigmentosa
. PLoS One
. 2018
;13
(12
):e0207958
. .9.
Weisschuh
N
, Obermaier
CD
, Battke
F
, Bernd
A
, Kuehlewein
L
, Nasser
F
, Genetic architecture of inherited retinal degeneration in Germany: a large cohort study from a single diagnostic center over a 9-year period
. Hum Mutat
. 2020
;41
(9
):1514
–27
. .10.
Bravo-Gil
N
, González-Del Pozo
M
, Martín-Sánchez
M
, Méndez-Vidal
C
, Rodríguez-de la Rúa
E
, Borrego
S
, Unravelling the genetic basis of simplex Retinitis Pigmentosa cases
. Sci Rep
. 2017
;7
:41937
. .11.
Huang
XF
, Wu
J
, Lv
JN
, Zhang
X
, Jin
ZB
. Identification of false-negative mutations missed by next-generation sequencing in retinitis pigmentosa patients: a complementary approach to clinical genetic diagnostic testing
. Genet Med
. 2015
;17
(4
):307
–11
. .12.
Eisenberger
T
, Neuhaus
C
, Khan
AO
, Decker
C
, Preising
MN
, Friedburg
C
, Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies
. PLoS One
. 2013
;8
(11
):e78496
. .13.
Birtel
J
, Gliem
M
, Oishi
A
, Müller
PL
, Herrmann
P
, Holz
FG
, Genetic testing in patients with retinitis pigmentosa: features of unsolved cases
. Clin Exp Ophthalmol
. 2019
;47
(6
):779
–86
. .14.
Sekimoto
M
, Hayasaka
S
, Noda
S
, Setogawa
T
. Pseudoretinitis pigmentosa in patients with systemic lupus erythematosus
. Ann Ophthalmol
. 1993
;25
(7
):264
–6
.15.
Lotery
AJ
, McBride
MO
, Larkin
C
, Sharkey
JA
. Pseudoretinitis pigmentosa due to sub-optimal treatment of neurosyphilis
. Eye
. 1996
;10
(Pt 6
):759
–60
. .16.
Heckenlively
JR
, Fawzi
AA
, Oversier
J
, Jordan
BL
, Aptsiauri
N
. Autoimmune retinopathy: patients with antirecoverin immunoreactivity and panretinal degeneration
. Arch Ophthalmol
. 2000
;118
(11
):1525
–33
. .17.
Makiyama
Y
, Kikuchi
T
, Otani
A
, Oishi
A
, Guo
C
, Nakagawa
S
, Clinical and immunological characterization of paraneoplastic retinopathy
. Invest Ophthalmol Vis Sci
. 2013
;54
(8
):5424
–31
. .18.
Marsiglia
M
, Duncker
T
, Peiretti
E
, Brodie
SE
, Tsang
SH
. Unilateral retinitis pigmentosa: a proposal of genetic pathogenic mechanisms
. Eur J Ophthalmol
. 2012
;22
(4
):654
–60
. .19.
Branham
K
, Schlegel
D
, Fahim
AT
, Jayasundera
KT
. Genetic testing for inherited retinal degenerations: triumphs and tribulations
. Am J Med Genet C Semin Med Genet
. 2020
;184
(3
):571
–7
. .20.
Shanks
ME
, Downes
SM
, Copley
RR
, Lise
S
, Broxholme
J
, Hudspith
KA
, Next-generation sequencing (NGS) as a diagnostic tool for retinal degeneration reveals a much higher detection rate in early-onset disease
. Eur J Hum Genet
. 2013
;21
(3
):274
–80
. .21.
Colombo
L
, Maltese
PE
, Castori
M
, El Shamieh
S
, Zeitz
C
, Audo
I
, Molecular epidemiology in 591 Italian probands with nonsyndromic retinitis pigmentosa and usher syndrome
. Invest Ophthalmol Vis Sci
. 2021
;62
(2
):13
. .22.
Marques
JP
, Carvalho
AL
, Henriques
J
, Murta
JN
, Saraiva
J
, Silva
R
. Design, development and deployment of a web-based interoperable registry for inherited retinal dystrophies in Portugal: the IRD-PT
. Orphanet J Rare Dis
. 2020
;15
(1
):304
. .23.
Popovic
P
, Jarc-Vidmar
M
, Hawlina
M
. Abnormal fundus autofluorescence in relation to retinal function in patients with retinitis pigmentosa
. Graefes Arch Clin Exp Ophthalmol
. 2005
;243
(10
):1018
–27
.24.
Hood
DC
, Lazow
MA
, Locke
KG
, Greenstein
VC
, Birch
DG
. The transition zone between healthy and diseased retina in patients with retinitis pigmentosa
. Invest Ophthalmol Vis Sci
. 2011
;52
(1
):101
–8
. .25.
Richards
S
, Aziz
N
, Bale
S
, Bick
D
, Das
S
, Gastier-Foster
J
, Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and genomics and the association for molecular pathology
. Genet Med
. 2015
;17
(5
):405
–24
. .26.
Koyanagi
Y
, Akiyama
M
, Nishiguchi
KM
, Momozawa
Y
, Kamatani
Y
, Takata
S
, Genetic characteristics of retinitis pigmentosa in 1204 Japanese patients
. J Med Genet
. 2019
;56
(10
):662
–70
. .27.
Zhao
L
, Wang
F
, Wang
H
, Li
Y
, Alexander
S
, Wang
K
, Next-generation sequencing-based molecular diagnosis of 82 retinitis pigmentosa probands from Northern Ireland
. Hum Genet
. 2015
;134
(2
):217
–30
. .28.
Xu
Y
, Guan
L
, Shen
T
, Zhang
J
, Xiao
X
, Jiang
H
, Mutations of 60 known causative genes in 157 families with retinitis pigmentosa based on exome sequencing
. Hum Genet
. 2014
;133
(10
):1255
–71
. .29.
Wang
J
, Zhang
VW
, Feng
Y
, Tian
X
, Li
FY
, Truong
C
, Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa
. Invest Ophthalmol Vis Sci
. 2014
;55
(10
):6213
–23
. .30.
Iutaka
NA
, Grochowski
RA
, Kasahara
N
. Correlation between visual field index and other functional and structural measures in glaucoma patients and suspects
. J Ophthalmic Vis Res
. 2017
;12
(1
):53
–7
. .31.
Costela
FM
, Pesudovs
K
, Sandberg
MA
, Weigel-DiFranco
C
, Woods
RL
. Validation of a vision-related activity scale for patients with retinitis pigmentosa
. Health Qual Life Outcomes
. 2020
;18
(1
):196
. .© 2021 S. Karger AG, Basel
2021
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
