UKGTN Testing Criteria Approved name and symbol of disease/condition(s): Retinal Degeneration panel test Approved name and symbol of gene(s): a panel of 105 genes, variants of which have been shown to be causative of Retinal Degeneration conditions OMIM number(s): OMIM number(s): Patient name: Patient postcode: Date of birth: NHS number: Name of referrer: Title/Position: Lab ID: Referrals will only be accepted from one of the following: Referrer Consultant Clinical Geneticists Consultant Ophthalmologist with special interest in retinal disorders Tick if this refers to you. Minimum criteria required for testing to be appropriate as stated in the Gene Dossier: Criteria The minimum criteria for acceptance is that the index case: has been diagnosed as a result of symptoms of initial rod dysfunction followed by peripheral cone dysfunction OR a characteristic retinal appearance OR characteristic ERG. X linked RP Autosomal Dominant RP Autosomal Recessive RP Sporadic Tick if this patient meets criteria Additional Information: Please note that if the diagnosis is probable/definite and there is a single gene test for that condition, the clinician may prefer to carry out the single gene test rather than the panel test. For example Retinoschisis (available from Cambridge), Stargardt (available from Oxford), Bardet Biedl (available from Great Ormond Street) and X-linked RP as single test available from Manchester If the sample does not fulfil the clinical criteria or you are not one of the specified types of referrer and you still feel that testing should be performed please contact the laboratory to discuss testing of the sample
Appendix 1 Conditions included in the panel Gene HGNC Phenotype Phenotype OMIM # Gene/locus OMIM # CA4 Retinitis pigmentosa 17 #600852 *114760 CERKL Retinitis pigmentosa 26 #608380 *608381 CNGA1 Retinitis pigmentosa 49 #613756 *123825 CNGB1 Retinitis pigmentosa 45 #613767 *600724 CRB1 Leber congenital amaurosis 8 #613835 *604210 Pigmented paravenous chorioretinal atrophy #172870 Retinitis pigmentosa 12, autosomal recessive #600105 CRX Cone rod retinal dystrophy 2 #120970 *602225 Leber congenital amaurosis 7 #613829 EYS Retinitis pigmentosa 25 #602772 *612424 FSCN2 Retinitis pigmentosa 30 #607921 *607643 GUCA1B Retinitis pigmentosa 48 #613827 *602275 IDH3B Retinitis pigmentosa 46 #612572 *604526 IMPDH1 Leber congenital amaurosis 11 #613837 *146690 Retinitis pigmentosa 10 #180105 KLHL7 Retinitis pigmentosa 42 #612943 *611119 MERTK Retinitis pigmentosa 38 #613862 *604705 NR2E3 Enhanced S cone syndrome #268100 *604485 Retinitis pigmentosa 37 #611131 NRL Retinal degeneration, autosomal recessive, clumped +162080 +162080 pigment type Retinitis pigmentosa 27 #613750 RP1 Retinitis pigmentosa 1 #180100 *603937 RP9 Retinitis pigmentosa 9 #180104 *607331 PDE6A Retinitis pigmentosa 43 #613810 *180071 PDE6B Night blindness, congenital stationary, autosomal #163500 *180072 dominant 2 Retinitis pigmentosa 40 #613801 PRCD Retinitis pigmentosa 36 #610599 *610598 PROM1 Cone rod dystrophy 12 #612657 *604365 Macular dystrophy, retinal, 2 #608051 Retinitis pigmentosa 41 #612095 Stargardt disease 4 #603786 PRPF3 Retinitis pigmentosa 18 #601414 *607301 PRPF31 Retinitis pigmentosa 11 #600138 *606419
PRPF8 Retinitis pigmentosa 13 #600059 *607300 PRPH2 Choriodal dystrophy, central areolar 2 #613105 *179605 Foveomacular dystrophy, adult onset, with choroidal #608161 neovascularization Macular dystrophy, patterned #169150 Macular dystrophy, vitelliform #608161 Retinitis pigmentosa 7 #608133 Retinitis pigmentosa, digenic #608133 Retinitis punctata albescens #136880 RGR Retinitis pigmentosa 44 #613769 *600342 RGS9 Bradyopsia #608415 *604067 RHO Night blindness, congenital stationery, autosomal #610445 *180380 dominant 1 Retinitis pigmentosa 4, autosomal dominant or #613731 recessive Retinitis punctata albescens #136880 RLBP1 Bothnia retinal dystrophy #607475 *180090 Fundus albipunctatus #136880 Newfoundland rod cone dystrophy #607476 Retinitis punctata albescens #136880 ROM1 Retinitis pigmentosa 7, digenic #608133 *180721 RP2 Retinitis pigmentosa 2 #312600 *300757 RPE65 Leber congenital amaurosis 2 #204100 *180069 Retinitis pigmentosa 20 #613794 RPGR* Cone rod dystrophy 1 #304020 *312610 Macular degeneration, X linked atrophic #300834 Retinitis pigmentosa 3 #300029 Retinitis pigmentosa, X linked, and sinorespiratory #300455 infections, with or without deafness SAG Oguchi disease 1 #258100 *181031 Retinitis pigmentosa 47 #613758 SEMA4A Cone rod dystrophy 10 #610283 *607292 Retinitis pigmentosa 35 #610282 TOPORS Retinitis pigmentosa 31 #609923 *609507 TTC8 Bardet Biedl syndrome 8 #209900 *608132 Retinitis pigmentosa 51 #613464 TULP1 Leber congenital amaurosis 15 #613843 *602280 Retinitis pigmentosa 14 #600132 CEP290 Bardet Biedl syndrome 14 #209900 *610142 Joubert syndrome 5 #610188 Leber congenital amaurosis 10 #611755 Meckel syndrome type 4 #611134 Senior Loken syndrome 6 #610189
AIPL1 Cone rod dystrophy #604393 *604392 Leber congenital amaurosis 4 #604393 Retinitis pigmentosa, juvenile #604393 GUCY2D Cone rod dystrophy 6 #601777 *600179 Leber congenital amaurosis 1 #204000 LCA5 Leber congenital amaurosis 5 #604537 *611408 LRAT Leber congenital amaurosis 14 #613341 *604863 Retinal dystrophy, early onset severe #613341 Retinitis pigmentosa, juvenile #613341 RD3 Leber congenital amaurosis 12 #610612 *180040 RDH12 Leber congenital amaurosis 13 #612712 *608830 SPATA7 Leber congenital amaurosis 3 #604232 *609868 Retinitis pigmentosa, juvenile, autosomal recessive #268000 ADAM9 Cone rod dystrophy 9 #612775 *602713 CACNA2D4 Retinal cone dystrophy 4 #610478 *608171 KCNV2 Retinal cone dystrophy 3B #610356 *607604 RIMS1 Cone rod dystrophy 7 #603649 *606629 RPGRIP1 Cone rod dystrophy 13 #608194 *605446 Leber congenital amaurosis 6 #613826 UNC119 Cone rod dystrophy +604011 +604011 C1QTNF5 Retinal degeneration, late onset, autosomal dominant #605670 *608752 BEST1 Best macular dystrophy #153700 *607854 Bestrophinopathy #611809 Microcornea, rod cone dystrophy, cataract, and #193220 posterior staphyloma Retinitis pigmentosa, concentric #613194 Retinitis pigmentosa 50 #613194 Vitelliform macular dystrophy, adult onset #608161 Vitreoretinochoroidopathy #193220 ABCA4 Cone rod dystrophy 3 #604116 *601691 Fundus flavimaculatus #248200 Macular degeneration, age related, 2 #153800 Retinal dystrophy, early onset severe #248200 Retinitis pigmentosa 19 #601718 Stargardt disease 1 #248200 CHM Choroideremia #303100 *300390 ELOVL4 Macular dystrophy, autosomal dominant, chromosome #600110 *605512 6 linked Stargardt disease 3 #600110 CNGA3 Achromatopsia 2 #216900 *600053 CNGB3 Achromatopsia 3 #262300 *605080 Macular degeneration, juvenile #248200 GNAT2 Achromatopsia 4 #613856 *139340 PDE6C Cone dystrophy 4 #613093 *600827 RS1 Retinoschisis #312700 *300839
FZD4 Exudative vitreoretinopathy #133780 *604579 Retinopathy of prematurity #133780 LRP5 Exudative vitreoretinopathy 4 #601813 *603506 NDP Exudative vitreoretinopathy, X linked #305390 *300658 Norrie disease #310600 GUCA1A Cone dystrophy 3 #602093 *600364 Cone rod dystrophy 14 #602093 TIMP3 Sorsby fundus dystrophy #136900 *188826 EFEMP1 Doyne honeycomb degeneration of retina #126600 *601548 RDH5 Fundus albipunctatus #136880 *601617 TEAD1 Sveinsson choreoretinal atrophy #108985 *189967 RAX2 Cone rod dystrophy 11 #610381 *610362 Macular degeneration, age related, 6 #613757 CLRN1 Retinitis pigmentosa 61 #614180 *606397 Usher syndrome, type 3A #276902 ARL6 Bardet Biedl syndrome 3 #209900 *608845 Retinitis pigmentosa 55 #613575 BBS1 Bardet Biedl syndrome 1 #209900 *209901 BBS10 Bardet Biedl syndrome 10 #209900 *610148 BBS12 Bardet Biedl syndrome 12 #209900 *610683 BBS2 Bardet Biedl syndrome 2 #209900 *606151 BBS4 Bardet Biedl syndrome 4 #209900 *600374 BBS5 Bardet Biedl syndrome 5 #209900 *603650 BBS7 Bardet Biedl syndrome 7 #209900 *607590 BBS9 Bardet Biedl syndrome 9 #209900 *607968 MKKS Bardet Biedl syndrome 6 #209900 *604896 McKusick Kaufman syndrome #236700 TRIM32 Bardet Biedl syndrome 11 #209900 *602290 DFNB31 Deafness, autosomal recessive 31 #607084 *607928 Usher syndrome, type 2D #611383 GPR98 Usher syndrome, type 2C #605472 *602851 PCDH15 Deafness, autosomal recessive 23 #609533 *605514 Usher syndrome, type 1D/F digenic #601067 Usher syndrome, type 1F #602083 USH2A Retinitis pigmentosa 39 #613809 *608400 Usher syndrome, type 2A #276901 CDH23 Deafness, autosomal recessive 12 #601386 *605516 Usher syndrome, type 1D #601067 Usher syndrome, type 1D/F digenic #601067 MYO7A Deafness, autosomal dominant 11 #601317 *276903 Deafness, autosomal recessive 2 #600060 Usher syndrome, type 1B #276900 USH1C Deafness, autosomal recessive 18 #602092 *605242 Usher syndrome, type 1C #276904 USH1G Usher syndrome, type 1G #606943 *607696 FAM161A Retinitis pigmentosa 28 #606068 *613596
C2orf71 Retinitis pigmentosa 54 #613428 *613425 IMPG2 Maculopathy, IMPG2 related #613581 *607056 Retinitis pigmentosa 56 #613581 PDE6G Retinitis pigmentosa 57 #613582 *180073 SNRNP200 Retinitis pigmentosa 33 #610359 *601664 RBP3 Autosomal Recessive Retinitis pigmentosa None given *180290 ZNF513 Retinitis pigmentosa 58 #613617 *613598 CDHR1 Cone rod dystrophy 15 #613660 *609502 RP1L1 Occult macular dystrophy #613587 *608581 OTX2 Microphthalmia, syndromic 5 #610125 *600037 Pituitary hormone deficiency, combined, 6 #613986 Retinal dystrophy, early onset, and pituitary #610125 dysfunction DHDDS Retinitis pigmentosa 59 #613861 *608172 PITPNM3 Cone rod dystrophy 5 #600977 *608921 MKS1 Bardet Biedl syndrome 13 #209900 *609883 Meckel syndrome, type 1 #249000 PRPF6 Retinitis pigmentosa 60 #613983 *613979 UNC119 Cone rod dystrophy +604011 +604011
Appendix 2 - Genes included in the next generation sequencing assay HGNC Transcript HGNC Transcript HGNC Transcript CA4 NM_000717.3 RLBP1 NM_000326.4 ELOVL4 NM_022726.3 CERKL NM_001030311.2 ROM1 NM_000327.3 CNGA3 NM_001298.2 CNGA1 NM_001142564.1 RP2 NM_006915.2 CNGB3 NM_019098.4 CNGB1 NM_001297.4 RPE65 NM_000329.2 GNAT2 NM_005272.3 CRB1 NM_201253.2 RPGR* NM_001034853.1 PDE6C NM_006204.3 CRX NM_000554.4 SAG NM_000541.4 RS1 NM_000330.3 EYS NM_001142800.1 SEMA4A NM_022367.3 FZD4 NM_012193.2 FSCN2 NM_001077182.2 TOPORS NM_005802.4 LRP5 NM_002335.2 GUCA1B NM_002098.5 TTC8 NM_144596.2 NDP NM_000266.3 IDH3B NM_006899.2 TULP1 NM_003322.3 GUCA1A NM_000409.3 IDH3B NM_174855.1 CEP290 NM_025114.3 TIMP3 NM_000362.4 IMPDH1 NM_000883.3 AIPL1 NM_014336.3 EFEMP1 NM_004105.3 KLHL7 NM_001031710.2 GUCY2D NM_000180.3 RDH5 NM_001199771.1 MERTK NM_006343.2 LCA5 NM_181714.3 TEAD1 NM_021961.5 NR2E3 NM_014249.2 LRAT NM_004744.3 RAX2 NM_032753.3 NRL NM_006177.3 RD3 NM_183059.2 CLRN1 NM_052995.2 RP1 NM_006269.1 RDH12 NM_152443.2 CLRN1 NM_001195794.1 RP9 NM_203288.1 SPATA7 NM_018418.4 ARL6 NM_032146.3 PDE6A NM_000440.2 ADAM9 NM_003816.2 BBS1 NM_024649.4 PDE6B NM_000283.3 CACNA2D4 NM_172364.4 BBS10 NM_024685.3 PRCD NM_001077620.2 KCNV2 NM_133497.3 BBS12 NM_001178007.1 PROM1 NM_006017.2 RIMS1 NM_014989.4 BBS2 NM_031885.3 PRPF3 NM_004698.2 RIMS1 NM_001168407.1 BBS4 NM_033028.3 PRPF31 NM_015629.3 RIMS1 NM_001168410.1 BBS5 NM_152384.2 PRPF8 NM_006445.3 RPGRIP1 NM_020366.3 BBS7 NM_176824.2 PRPH2 NM_000322.4 UNC119 NM_005148.3 BBS7 NM_018190.3 RGR NM_002921.3 C1QTNF5 NM_015645.3 BBS9 NM_198428.2 RGS9 NM_003835.3 BEST1 NM_004183.3 MKKS NM_018848.2 RGS9 NM_001165933.1 ABCA4 NM_000350.2 TRIM32 NM_012210.3 RHO NM_000539.3 CHM NM_000390.2 DFNB31 NM_015404.3 GPR98 NM_032119.3 CDH23 NM_022124.5 IMPG2 NM_016247.2 PCDH15 NM_001142763.1 MYO7A NM_000260.3 PDE6G NM_002602.3 PCDH15 NM_001142769.1 USH1C NM_005709.3 SNRNP200 NM_014014.3 PCDH15 NM_001142770.1 USH1C NM_153676.3 RBP3 NM_002900.2 PCDH15 NM_001142771.1 USH1G NM_173477.2 ZNF513 NM_144631.5 USH2A NM_206933.2 FAM161A NM_001201543.1 CDHR1 NM_001171971.1 RP1L1 NM_178857.5 PITPNM3 NM_031220.3 MKS1 NM_001165927.1 OTX2 NM_021728.2 MKS1 NM_017777.3 PRPF6 NM_012469.3 DHDDS NM_024887.2 Notes: (1) For some genes the analysis of multiple transcripts is required. (2) * For RPGR it is not possible to obtain high quality read for exon ORF15. Consequently this analysis is offered separately on request further details are available at: http://www.mangen.co.uk/professionals/services/servicedetails/x-linked+retinitis+pigmentosa.aspx
Appendix 3 - Test strategy Test Criteria Clearly X linked Other referral indication ORF 15 test 105 gene panel test ORF 15 mutation Report No ORF 15 mutation (an additional request is required from referring clinician) Report