Complete Panel of Retinal Dystrophies and other eye diseases

The DBGen complete panel allows analyzing 346 genes and 66 intronic regions that contain mutations that cause retinal dystrophies and the most frequent macular dys- trophies, and also other ophthalmological diseases. This test identifies point muta- tions (SNVs) and genomic rearrangements due to duplications and deletions (CNVs), thus yielding an average coverage over 500x. This in-depth analysis ensures diagnos- tic quality and success at an excellent cost/effectiveness ratio.

ABOUT RETINAL DYSTRO- roideremia, COACH syndrome, Cohen syndrome, PHIES AND OTHER EYE DI- Cone-rod dystrophy, Congenital stationary night blindness, Costeff optic atrophy syndrome, Doyne SEASES honeycomb degeneration of , Enhanced S-co- ne syndrome, Exudative vitreoretinopathy, Familial This is a set of degenerative di- benign fleck retina, Albipunctatus, Glauco- seases of the retina and optic ma, Hermansky-Pudlak syndrome, Jalili syndrome, nerve that exhibit a wide gene- , Knobloch syndrome, Leber con- tic and clinical heterogeneity. genital amaurosis, Mainzer-Saldino syndrome, Mc- These diseases can be stationary Kusick-Kaufman syndrome, Meckel syndrome, Me- valonate deficiency, Nephronophthisis, Norrie or progressive from an early age. disease, Oculocutaneous albinism, Oguchi disease, They can also occur in isolation Open-angle , Optic atrophy, or in syndromic forms. The inhe- hypoplasia, Peters anomaly, Pigmented paravenous ritance pattern can be autoso- chorioretinal atrophy, Refsum disease, pig- mal dominant, autosomal reces- mentosa, , Rhegmatogenous retinal sive or X-linked. Over 300 genes detachment, Senior-Loken syndrome, Sorsby Fun- are known to cause these types dus Dystrophy, , Stickler syndrome, of disorders, most of them affec- Usher syndrome, Vitelliform macular dystrophy type ting the expression of proteins I, Vitelliform macular dystrophy type II, Vitreoretino- choroidopathy, Waardenburg syndrome, Wagner sy- involved in phototransduction, ndrome the structure of photoreceptors and the cellular pathways nee- RESULTS ded for viability and function in A detailed genetic report that includes the ge- retinal cell. Moreover, mutations netic variants identified and genetic counse- in the same gene can cause di- ling will be provided. Supporting information fferent pathologies. will be exhaustive based on bibliographical studies and database analyses and, especially, PATHOLOGIES on our 25 years of experience researching the The panel includes the genes genetics of hereditary eye diseases. most often responsible for the following pathologies: The test will be performed once payment is made and the signed informed consent and , Albinism, Alström the sample are received. The report will be syndrome, , Axenfeld-Rieger syndrome, Bardet-Biedl syndrome, delivered 12 to 14 weeks after the above condi- Bestrophinopathy, Bietti crystalline tions are satisfied. dystrophy, Bosch-Boonstra-Schaaf opticatrophy syndrome, Bothnia re- PRICE tinal dystrophy, Bradyopsia, Central From €950. Please contact us to know the op- areolar choroidal dystrophy, Cho- tions that best suit your needs.

www.dbgen.com METHODOLOGY CA4, CABP4, CACNA1F, CACNA2D4, CAPN5, CC2D2A, CDH16, CDH23, CDH3, CDHR1, CEP19, CEP164, CEP250, CEP290, CEP41, CEP78, The diagnostic strategy relies CEP83, CERKL, CFH, CHM, CIB2, CLCC1, CLN3, CLRN1, CLUAP1, on the automated sequencing CNGA1, CNGA3, CNGB1, CNGB3, CNNM4, COL11A1, COL11A2, COL18A1, COL2A1, COL4A1, COL4A3, COL4A4, COL4A5, COL9A1, COL9A2, CO- of DNA on Illumina HiSeq 2000 L9A3, CRB1, CRYAA, CRYBA4, CRX, CSPP1, CTNNA1, CWC27, CYP1B1, sequencers that are specially de- CYP4V2, DFNB31, DHDDS, DHX38, DNAJC17, DNM1L, DRAM2, signed for this kind of high-per- DTHD1, DTNBP1, EDN3, EDNRB, EFEMP1, ELOVL4, EMC1, ESPN, EYS, FAM161A, FLVCR1, FOXC1, FRMD7, FSCN2, FZD4, GDF6, GLIS2,G- formance analysis. Our panels NAT1, GNAT2, GNB3, GPR125, GPR143, GPR179, GPR98, GRK1, GRM6, have been designed to prioritize GUCA1A, GUCA1B, GUCY2D, GYLTL1B, HARS, HESX1, HGSNAT, HK1, HPS1, HPS3, HPS4, HPS5, HPS6, IDH3A, IDH3B, IFT43, IFT80, IFT140, the genomic regions associated IFT172, IFT27, IFT81, IMPDH1, IMPG1, IMPG2, INPP5E, INVS, IQCB1, with the hereditary eye diseases IRX1, JAG1, KCNJ13, KCNV2, KIAA1549, KIF11, KIZ, KLHL7, LCA5, LMX1B, LRAT, LRIT3, LRP5, LTBP2, LZTFL1, MAK, MAPKAPK3, MC1R, MERTK, indicated in this text. MFN2, MFRP, MFSD8, MITF, MIR204, MKKS, MKS1, MVK, MYO7A, MYOC, NDP, NEK2, NEK8, NEUROD1, NMNAT1, NPHP1, NPHP3, The likely pathogenic nucleo- NPHP4, NR2E3, NR2F1, NRL, NYX, OAT, OCA2, OFD1, OPA1, OPA3, OP- N1LW, OPN1MW, OPN1SW, OPTN, OTX2, PANK2, PAX2, PAX3, PAX6, tide variants are verified using PCDH15, PCYT1A, PDE6A, PDE6B, PDE6C, PDE6D, PDE6G, PDE6H, Sanger sequencing. We check PDZD7, PEX1, PEX2, PEX7, PHYH, PITPNM3, PITX2, PLA2G5, PLG, PLK4, POC1B, POC5, POLG, POMGNT1, PNPLA6, PRCD, PRDM13, that their frequency in the con- PROKR2, PROM1, PRPF3, PRPF31, PRPF4, PRPF6, PRPF8, PRPH2, trol population is below 1% and PRPS1, RAB28, RAX2, RB1, RBP3, RBP4, RCBTB1, RD3, RDH11, RDH12, RDH5, REEP6, RGR, RGS9, RGS9BP, RHO, RIMS1, RLBP1, ROM1, RP1, that they meet the pathogenici- RP1L1, RP2, RP9, RPE65, RPGR, RPGRIP1, RPGRIP1L, RS1, RTN4IP1, ty predictions as per established SAG, SAMD11, SCAPER, SCLT1, SCN2A, SDCCAG8, SEMA4A, SEMA6B, bioinformatics algorithms (SIFT, SH3PXD2B, SLC24A1, SLC24A5, SLC25A46, SLC38A8, SLC45A2, SL- C4A3, SLC7A14, SNAI2, SNRNP200, SOX10, SOX2, SOX3, SPATA7, SPP2, LRT, MutationTaster, PolyPhen2, STRA6, SYT9, TCTN1, TCTN2, TCTN3, TEK, TIMM8A, TIMP3, TMEM107, CADD and NetGene2). TMEM126A, TMEM138, TMEM216, TMEM231, TMEM237, TMEM67, TMPRSS4, TOPORS, TPP1, TRAF3IP1, TREX1, TRIM32, TRNT1, TRPM1, TSPAN12, TSPAN6, TTC21B, TTC8, TTLL5, TTPA, TTR, TUB, TUBGCP4, TUBGCP6, TULP1, TYR, TYRP1, UCHL1, UNC119, USH1C, USH1G, US- RECOMMENDED FOR H2A, VCAN, VHL, VPS13B, WDPCP, WDR19, WDR36, WFS1, ZNF408, This test is recommended when ZNF423, ZNF513. the clinical diagnosis indicates a disease of the retina or optic And 66 relevant intronic regions of 13 genes: nerve in both syndromic and non-syndromic cases, and es- ABCA4 (all introns), CEP290 c.2991+1655A>G, CHM c.315-4587T>A, CHM c.315-1536A>G, COL2A1 c.1527+104T>G, COL2A1 c.1527+135G>A, pecially when the clinical condi- COL4A5 c.2395+2750A>G, COL4A5 c.385-719G>A, COL4A3 c.4929- tions are not clearly defined. 388G>T, GPR143 c.659-131T>G, OFD1 c.935+706A>G, OPA1 c.610+- 360G>A, OPA1 c.610+364G>A, PRPF31 c.1374+654C>G, RB1 c.2490- 1398A>G, USH2A c.7595-2144A>G, RPGRIP1 promotor, USH2A This panel offers a very high c.8845+628C>T, USH2A c.9959-4159A>G, USH2A c.5573-834A>G diagnostic yield (>79%) as it in- cludes a high number of cau- sative genes and because the method used allows identifying some structural genomic alte- rations difficult to characterize with other test types.

GENES ANALYZED Simultaneously sequence of all the coding regions (exons) of 346 genes

ABCA4, ABCC6, ABHD12, ACBD5, ACO2, ADAM9, ADAMTS18, ADIPOR1, AGBL5, AHI1, AHR, AIPL1, ALMS1, ANKS6, AP3B1, ARHGEF18, ARL13B, ARL2BP, ARL3, ARL6, ARSG, ASB10, ASRGL1, ATF6, B9D1, B9D2, BBIP1, BBS1, BBS10, BBS12, BBS2, BBS4, BBS5, BBS7, BBS9, BEST1, BLOC1S3, BLOC1S6, BTD, C10orf11, C12orf65, C1QTNF5, C21orf2, C2orf71, C5orf42, C8orf37,

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