1. NGS panel - Genetic testing for retinitis pigmentosa

Retinitis pigmentosa

June 22, 2017

Disease synonyms

Nonsyndromic Retinitis Pigmentosa, Autosomal recessive retinitis pigmentosa, arRP, Nonsyndromic Retinitis Pigmentosa, Autosomal dominant retinitis pigmentosa, adRP

Inheritance pattern

Autosomal recessive, autosomal dominant


Clinical features

Retinitis pigmentosa (RP) refers to a group of rare inherited diseases characterized by abnormalities of the photoreceptors of the retina, leading to progressive visual loss. The prevalence of retinitis pigmentosa is 1:3000 to 1:7000 persons, or 14 to 33 per 100,000 1.

Retinitis pigmentosa that does not affect other organs or tissues is classified as non-syndromic or “simple” and if it is associated with neurosensory systems such as hearing it is classified as systemic retinitis pigmentosa 2. Nonsyndromic retinitis pigmentosa can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Rare digenic forms also occur (for example in individuals who are heterozygous for both a ROM1 pathogenic variant and a PRPH2 pathogenic variant) 3.

The most common clinical features of retinitis pigmentosa include the following 1:

  • Night blindness or defective adaptation to dark, also known as nyctalopia
  • Visual acuity e.g. early loss of cone function, resulting in loss of central visual acuity over time
  • Cystoid macular edema (CME) is estimated to occur in approximately 10-50% of individuals with RP, depending on the study, the genetic type, and the diagnostic tool 1, 13
  • Fundus appearance: the earliest observed changes in the fundus are arteriolar narrowing, fine dust-like intraretinal pigmentation, and loss of pigment from the pigment epithelium
  • Moderate to severe retinal vessel attenuation and waxy pallor of the optic nerve
  • Posterior subcapsular cataracts characterized by yellowish crystalline changes in the visual axis of the posterior lens cortex
  • Dust-like particles in the vitreous
  • Hyaline bodies of the optic nerve head
  • Exudative vasculopathy, known also as Coats-like disease.

The diagnosis of retinitis pigmentosa is established based on the level of rod dysfunction, intensity of photoreceptor function loss and loss of peripheral vision, as well as a positive family history of retinal disease. Retinitis pigmentosa can be inherited in autosomal dominant (adRP: 15-25%), autosomal recessive (arRP: 5-20%), X-linked (xlRP: 5-15%), and digenic fashion (rare)1.

The genes associated with nonsyndromic autosomal recessive retinitis pigmentosa (arRP) are listed in Table 1, while the genes associated with autosomal dominant forms of retinitis pigmentosa are listed in Table 2.

There is no cure for retinitis pigmentosa, however measures are available to help patients, including vitamin A/beta-carotene and antioxidans in general. Macular edema can be reduced using acetazolamide, lutein, and other drugs.

CENTOGENE offers sequencing and deletion/duplication analysis for the following panels:

Retinitis pigmentosa panel, autosomal recessive (ABCA4, ARL6, BBS1, BEST1, C2ORF71, C8ORF37, CERKL, CNGA1, CNGB1, CRB1, DHDDS, EYS, FAM161A, FLVCR1, GNPTG, IDH3B, IMPG2, LRAT, MAK, MERTK, NR2E3, NRL, PDE6A, PDE6B, PDE6G, PRCD, PROM1, RBP3, RDH12, RGR, RHO, RLBP1, RP1, RP2, RPE65, RPGR, SAG, SEMA4A, SPATA7, TTC8, TULP1, USH2A, ZNF513)

Retinitis pigmentosa panel, autosomal dominant (ABCA4, BEST1, CA4, CRX, CLRN1, FSCN2, GUCA1B, IMPDH1, KLHL7, NR2E3, NRL, PRPF3, PRPF31, PRPF6, PRPF8, PRPH2, RDH12, RGR, RHO, ROM1, RP1, RP2, RP9, RPE65, RPGR, SEMA4A, SNRNP200, TOPORS.


Table 1: Overview of genes included in Retinis pigmentosa panel, autosomal recessive

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ABCA4 601691 Macular degeneration, age-related, 2; Fundus flavimaculatus; Retinal dystrophy, early-onset severe; Stargardt disease 1; Retinitis pigmentosa 19; Cone-rod dystrophy 3 AD, AR 64
ARL6 608845 Bardet-Biedl syndrome 1, modifier of; Bardet-Biedl syndrome 3; ?Retinitis pigmentosa 55 AR, Digenic R 6
BBS1 209901 Bardet-Biedl syndrome 1 AR, Digenic R 14
BEST1 607854 Macular dystrophy, vitelliform, 2; Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma; Vitreoretinochoroidopathy; Bestrophinopathy, autosomal recessive; Retinitis pigmentosa, concentric; Retinitis pigmentosa-50 AD 31
C2orf71 613425 Retinitis pigmentosa 54 4
C8orf37 614477 Cone-rod dystrophy 16; Retinitis pigmentosa 64; Bardet-Biedl syndrome 21 AR 3
CERKL 608381 Retinitis pigmentosa 26 11
CNGA1 123825 Retinitis pigmentosa 49 11
CNGB1 600724 Retinitis pigmentosa 45 AR 25
CRB1 604210 Pigmented paravenous chorioretinal atrophy; Retinitis pigmentosa-12, autosomal recessive; Leber congenital amaurosis 8 AD, AR 10
DHDDS 608172 ?Congenital disorder of glycosylation, type 1bb; Retinitis pigmentosa 59; Developmental delay and seizures with or without movement abnormalities AD, AR 2
EYS 612424 Retinitis pigmentosa 25 AR 42
FAM161A 613596 Retinitis pigmentosa 28 6
FLVCR1 609144 Ataxia, posterior column, with retinitis pigmentosa AR 24
GNPTG 607838 Mucolipidosis III gamma AR 6
IDH3B 604526 Retinitis pigmentosa 46 6
IMPG2 607056 Retinitis pigmentosa 56; Macular dystrophy, vitelliform, 5 AD, AR 10
LRAT 604863 Leber congenital amaurosis 14; Retinal dystrophy, early-onset severe; Retinitis pigmentosa, juvenile AR 0
MAK 154235 Retinitis pigmentosa 62 AR 8
MERTK 604705 Retinitis pigmentosa 38 AR 25
NR2E3 604485 Enhanced S-cone syndrome; Retinitis pigmentosa 37 AD, AR 7
NRL 162080 Retinitis pigmentosa 27 AD 0
PDE6A 180071 Retinitis pigmentosa 43 23
PDE6B 180072 Night blindness, congenital stationary, autosomal dominant 2; Retinitis pigmentosa-40 AD, AR 14
PDE6G 180073 Retinitis pigmentosa 57 AR 5
PRCD 610598 Retinitis pigmentosa 36 9
PROM1 604365 Stargardt disease 4; Macular dystrophy, retinal, 2; Retinitis pigmentosa 41; Cone-rod dystrophy 12 AD, AR 30
RBP3 180290 ?Retinitis pigmentosa 66 AR 3
RDH12 608830 Leber congenital amaurosis 13 AR 7
RGR 600342 Retinitis pigmentosa 44 6
RHO 180380 Retinitis punctata albescens; Night blindness, congenital stationary, autosomal dominant 1; Retinitis pigmentosa 4, autosomal dominant or recessive AD, AR 1
RLBP1 180090 Fundus albipunctatus; Retinitis punctata albescens; Bothnia retinal dystrophy; Newfoundland rod-cone dystrophy AD, AR 3
RP1 603937 Retinitis pigmentosa 1 AD, AR 3
RP2 300757 Retinitis pigmentosa 2 XL 3
RPE65 180069 Leber congenital amaurosis 2; Retinitis pigmentosa 20 AR 7
RPGR 312610 Retinitis pigmentosa 3; Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness; Macular degeneration, X-linked atrophic; Cone-rod dystrophy, X-linked, 1 XL, XL R 22
SAG 181031 Oguchi disease-1; Retinitis pigmentosa 47 AR 12
SEMA4A 607292 Retinitis pigmentosa 35; Cone-rod dystrophy 10 AD, AR 7
SPATA7 609868 Leber congenital amaurosis 3; Retinitis pigmentosa, juvenile, autosomal recessive 14
TTC8 608132 ?Retinitis pigmentosa 51; Bardet-Biedl syndrome 8 AR 11
TULP1 602280 Retinitis pigmentosa 14; Leber congenital amaurosis 15 AR 20
USH2A 608400 Usher syndrome, type 2A; Retinitis pigmentosa 39 AR 51
ZNF513 613598 ?Retinitis pigmentosa 58 AR 3

Table 2: Overview of genes included in Retinis pigmentosa panel, autosomal dominant

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ABCA4 601691 Macular degeneration, age-related, 2; Fundus flavimaculatus; Retinal dystrophy, early-onset severe; Stargardt disease 1; Retinitis pigmentosa 19; Cone-rod dystrophy 3 AD, AR 64
BEST1 607854 Macular dystrophy, vitelliform, 2; Microcornea, rod-cone dystrophy, cataract, and posterior staphyloma; Vitreoretinochoroidopathy; Bestrophinopathy, autosomal recessive; Retinitis pigmentosa, concentric; Retinitis pigmentosa-50 AD 31
CA4 114760 Retinitis pigmentosa 17 AD 2
CLRN1 606397 Usher syndrome, type 3A; Retinitis pigmentosa 61 AR 2
CRX 602225 Cone-rod retinal dystrophy-2; Leber congenital amaurosis 7 AD 6
FSCN2 607643 Retinitis pigmentosa 30 3
GUCA1B 602275 Retinitis pigmentosa 48 3
IMPDH1 146690 Retinitis pigmentosa 10; Leber congenital amaurosis 11 AD 8
KLHL7 611119 Retinitis pigmentosa 42; Cold-induced sweating syndrome 3 AD, AR 9
NR2E3 604485 Enhanced S-cone syndrome; Retinitis pigmentosa 37 AD, AR 7
NRL 162080 Retinitis pigmentosa 27 AD 0
PRPF3 607301 Retinitis pigmentosa 18 AD 5
PRPF31 606419 Retinitis pigmentosa 11 AD 10
PRPF6 613979 Retinitis pigmentosa 60 AD 6
PRPF8 607300 Retinitis pigmentosa 13 AD 17
PRPH2 179605 Retinitis punctata albescens; Macular dystrophy, patterned, 1; Leber congenital amaurosis 18; Retinitis pigmentosa 7 and digenic; Macular dystrophy, vitelliform, 3; Choroidal dystrophy, central areolar 2 AD, AR 8
RDH12 608830 Leber congenital amaurosis 13 AR 7
RGR 600342 Retinitis pigmentosa 44 6
RHO 180380 Retinitis punctata albescens; Night blindness, congenital stationary, autosomal dominant 1; Retinitis pigmentosa 4, autosomal dominant or recessive AD, AR 1
ROM1 180721 Retinitis pigmentosa 7, digenic AD, AR 4
RP1 603937 Retinitis pigmentosa 1 AD, AR 3
RP2 300757 Retinitis pigmentosa 2 XL 3
RP9 607331 ?Retinitis pigmentosa 9 AD 3
RPE65 180069 Leber congenital amaurosis 2; Retinitis pigmentosa 20 AR 7
RPGR 312610 Retinitis pigmentosa 3; Retinitis pigmentosa, X-linked, and sinorespiratory infections, with or without deafness; Macular degeneration, X-linked atrophic; Cone-rod dystrophy, X-linked, 1 XL, XL R 22
SEMA4A 607292 Retinitis pigmentosa 35; Cone-rod dystrophy 10 AD, AR 7
SNRNP200 601664 Retinitis pigmentosa 33 AD 9
TOPORS 609507 Retinitis pigmentosa 31 2


Differential diagnosis

The differential diagnosis of retinitis pigmentosa-related disorders – depending on the major symptoms in the initial case – includes the following diseases:

  • Usher syndrome (types 1, 2, and 3)
  • Gyrate atrophy of the choroid and retina
  • Leber congenital amaurosis (LCA)
  • Cone or cone-rod dystrophy
  • Congenital disorders of glycosylation (CDG) type 1a
  • Best Disease
  • Central Serous Chorioretinopathy
  • Chronic Progressive External Ophthalmoplegia
  • Nonexudative (Dry) Age-Related Macular Degeneration (AMD)

Testing strategy

To confirm/establish the diagnosis, we offer retinitis pigmentosa panel sequencing and deletion/duplication gene testing. We also offer a broad selection of NGS panels that are designed for the molecular diagnostics of related conditions/phenotypes.

Thus, CENTOGENE offers the following testing strategy for retinitis pigmentosa gene testing

Step 1: Depending on the inheruitance mode:
Retinitis pigmentosa panel, autosomal recessive sequencing – covers the entire coding region, exon/intron boundaries and 200 bp of the gene promoter for all the genes included in the panel.
Retinitis pigmentosa panel, autosomal dominant sequencing – covers the entire coding region, exon/intron boundaries and 200 bp of the gene promoter for all the genes included in panel

Step 2: Deletion/duplication analysis/mutational scanning of selected retinitis pigmentosa panel genes.

Step 3: If no mutation is identified after analysis with the retinitis pigmentosa panel we can offer further whole genome sequencing, based on NGS technology.


Referral reasons

The following individuals are candidates for retinitis pigmentosa testing:

  • - Individuals with a family history of retinitis pigmentosa and presentation of the most common symptoms, including night blindness and loss of visual acuity
  • Individuals without a positive family history, but with symptoms resembling retinitis pigmentosa
  • Individuals with a negative but suspected family history of retinitis pigmentosa, in order to perform proper genetic counseling.

Test utility

Sequencing, deletion/duplication of the panel genes should be performed in all individuals suspected of having retinitis pigmentosa and suspected phenotypes. In parallel, other genes reported to be related with this clinical phenotype should also be analyzed for the presence of mutations, due to the overlap in many clinical features caused by those particular genes.

Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family with the natural history of the retinitis pigmentosa and related disorders identify at-risk family members, provide disease risks as well as appropriate referral for patient support and/or resources.


More information on CENTOGENE´s Retinitis pigmentosa panel, autosomal dominant and autosomal recessive can be found in our genetic test catalogue.