Retinal Degeneration Conditions

Introduction

We offer a comprehensive next generation sequencing mutation scan of 176 genes known to cause inherited retinal disease including an interpretation of variants found.

Referral information

We offer mutation scanning in affected individuals and obligate carriers. This testing is relevant for sporadic cases or patients with a family history consistent with an autosomal dominant, recessive or X-linked family history of retinal degeneration. Given the nature of the genes analysed this test is also appropriate for patients with macular dystrophy, achromatopsia, congenital stationary night blindness as well as Usher, Bardet-Biedl, Joubert, Senior-Loken and Cohen syndromes. Testing of family members may be required to help interpret our findings. On identification of a pathogenic change in an index case presymptomatic and carrier testing of relevant relatives of the proband can be offered. Referrals should be accompanied by a clinical diagnosis and details of family history. Referrals should also be accompanied by a completed standard referral request form and a completed NGS clinical proforma. Note that this test does not include RPGR ORF15; if this test is required please indicate on the referral. At present, NGS technology will not reliably detect large deletions and duplications. The current test service for the X-linked form of RD remains available (see our Ophthalmic Genetics page).

Technical information

The assay covers the known genes that cause: isolated progressive retinal degeneration; Leber congenital amaurosis; macular dystrophy; achromatopsia; congenital stationary night blindness as well as the two most common causes of syndromic blindness, Usher and Bardet-Biedl syndromes, and additional syndromes including Joubert, Senior-Loken and Cohen syndromes. The coding sequence of 176 genes, previously described in retinal dystrophy, are covered in the enrichment. Samples are sequenced on the Illumina HiSeq 2500 system. We undertake a complete bioinformatic analysis to highlight variants with a high likelihood of pathogenicity which are subsequently confirmed using conventional Sanger sequencing. On completion of the analysis a clinical report is issued incorporating a clinical interpretation of all pathogenic variants identified. In addition a summary of the coverage of the analysis and a full list of (non-validated) variants identified during the NGS screen are presented in the notes section of the clinical report. Confirmation of variants of uncertain clinical significance identified by the next generation sequencing screen is available on request at an extra charge.

Price & reporting times

Please contact the lab for prices.

Test Price (£ ex VAT) TRT *
Scan for 176 RD genes POA 112 cd

Test validation & quality assurance - information for users

In a validation series of 50 patients the mutation detection rate was 60% for ADRP patients, 60% for patients with a clear X-linked family history, 30% for patients likely to have recessive disease and 30% for sporadic cases. >97% of target exons are covered at 50x depth or more. The laboratory is UKAS assessed against ISO 15189 standards.

Sample requirements

Pre-natal: amniotic fluid (minimum 15ml)/chorionic villus biopsy (CVB) (minimum 10mg) sample plus 4ml EDTA maternal blood sample

Post-natal: 4ml EDTA blood sample

Referral guidelines

Please see our referral guidelines for more information.

OMIM Number(s) - 114760, 608381, 123825, 600724, 604210, 602225, 612424, 607643, 602275, 604526, 146690, 611119, 604705 , 604485, 162080, 603937, 607331, 180071, 180072, 610598, 604365, 607301 , 606419 , 607300 , 179605, 600342, 604067, 180380, 180090, 180721 , 300757, 180069, 312610, 181031, 607292, 609507, 608132, 602280, 610142, 604392, 600179, 611408, 604863, 180040, 608830, 609868, 602713, 608171, 607604 , 606629, 605446, 608752, 607854, 601691, 300390 , 605512, 600053 , 605080, 139340 , 600827, 300839 , 604579, 603506 , 300658, 600364, 188826, 601548, 601617, 189967, 610362, 606397, 608845, 209901 , 610148 , 610683 , 606151, 600374 , 603650, 607590 , 607968, 604896, 602290 , 607928, 602851 , 605514, 608400, 605516, 276903, 605242, 607696 , 613596 , 613425 , 607056, 180073 , 601664 , 180290 , 613598 , 609502 , 608581 , 600037, 608172 ,608921 , 609883, 613979 , 604011, 139330, 603576, 608965, 300110, 604096, 300278 , 603617, 614515, 607100, 609237, 613524, 607817, 613138, 142992, 606227, 607042, 613349, 601757 , 601757, 614477, 608700, 603208 , 607805, 608894 , 612013, 601192, 602870, 612994, 615407, 613605, 606568, 606568, 243305, 613037, 148760, 180250, 602537, 614848, 251170, 603904, 605564, 607838 , 614620 , 604557, 610937 , 114021 ,607512, 606157 , 603191, 300170, 607215, 602201, 609144, 613580, 613599, 614423, 608002, 612303, 608151, 608614, 118661, 142810, 602136, 613344, 170993, 123695,611654, 601197

Gene(s) - ABCA4; ABHD12; ACBD5; ADAM9; ADAMTS18; AHI1; AIPL1; ARL2BP; ARL6; BBIP1; BBS1; BBS10; BBS12; BBS2; BBS4; BBS5; BBS7; BBS9; BEST1; C1QTNF5; C2orf71; C2ORF86/(WDPCP); C8ORF37; C21orf2; CA4; CABP4; CACNA1F; CACNA2D4; CAPN5; CC2D2A ; CDH3; CDH23; CDHR1; CEP164; CEP290; CERKL; CHM; CIB2; CLN3; CLRN1; CNGA1; CNGA3; CNGB1; CNGB3; CNNM4; CRB1; CRX; CSPP1; CYP4V2; DFNB31; DHDDS; DTHD1; EFEMP1; ELOVL4; EMC1; EYS; FAM161A; FLVCR1; FSCN2; FZD4; GNAT1; GNAT2; GNPTG; GPR125; GPR179; GPR98; GRM6; GUCA1A; GUCA1B; GUCY2D; HARS; HMX1; IDH3B; IFT140; IMPDH1; IMPG1; IMPG2 7; INPP5E; INVS; IQCB1; ITM2B; KCNJ13; KCNV2; KIAA1549; KIF11; KLHL7; LCA5; LRAT; LRP5; LZTFL1; MERTK; MFRP; MKKS; MKS1; MVK; MYO7A; NDP; NEK2; NMNAT1; NPHP1; NPHP3; NPHP4; NR2E3; NRL; NYX; OAT; OFD1; OTX2; PANK2; PCDH15; PCYT1A; PDE6A; PDE6B; PDE6C; PDE6G; PEX1; PEX2/(PXMP3); PEX7; PHYH; PITPNM3; PLA2G5; PRCD; PROM1; PRPF3; PRPF31; PRPF4; PRPF6; PRPF8; PRPH2; RAB28; RAX2; RBP3; RBP4; RD3; RDH12; RDH5; RGR; RGS9; RHO; RIMS1; RLBP1; ROM1; RP1; RP1L1 (excluding exon 4); RP2; RP9; RPE65; RPGR (excluding ORF15); RPGRIP1; RPGRIP1L; RS1; SAG; SDCCAG8; SEMA4A; SLC24A1; SNRNP200; SPATA7; TEAD1; TIMP3; TMEM237; TOPORS; TRIM32; TRPM1; TSPAN12; TTC8; TUB ; TULP1; UNC119; USH1C; USH1G; USH2A; VCAN; VPS13B; WDR19; ZNF423; ZNF513

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