Cone-Rod Dystrophy 19

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

CRX, PROM1, ABCA4, GUCY2D, RPGR, GUCA1A, C8orf37, CDHR1, RPGRIP1, RIMS1, PRPH2, RAB28, ADAM9, POC1B, NMNAT1, AIPL1, PITPNM3, CNGA3, UNC119, SEMA4A, CACNA1F, CFAP410, CACNA2D4, ATF6, OPN1MW, TTLL5, DRAM2, RAX2, OPN1LW, H6PD, HSD11B1, AQP4, ALMS1, ATXN7, CNNM4, BDNF, GFAP, SOD1, IL6, NTF3, TST, CD6, CERKL, TNF, CSF3, CEP250, MIR137, GUCA2A, CORD1, TLR4, TNFRSF1B, VCP, IL1B, PTPRC, LAMC2, PRPH, POMC, SAR1B, NGF, NOS3, CSF2, TARDBP, CST3, GDNF, FGF2, ERG, EYS, GAP43, SMN2, CRB1, CTNNB1, C9orf72, RDH12, SMN1, CNTN6, GDE1, LEF1, PSIP1, IFT81, GIT1, HDAC3, SLC25A37, LPAR3, SNURF, CORD8, SLC35A1, SIGLEC7, MSC, RNU1-1, STMN2, ABCG2, LYVE1, NISCH, ADAMTS3, GAL3ST1, ADAMTS4, SNX27, TREM1, AHI1, NCR3, MRGPRX1, COPD, AMIGO3, HES5, PCARE, MIR15A, MIR17, MIR185, MIR20A, MIR21, MIR210, MIR219A1, MIR223, MIR30A, MIR31, VN1R17P, GPR166P, MIR372, MIR375, MIR409, MIR3074, CST12P, MFSD8, GPRC6A, ADAMTS18, CEP290, CASZ1, SPATA7, CCL28, KCNQ5, SAR1A, RGMA, NLN, LGR6, MICAL1, MAP9, LINGO1, KCNV2, MRGPRX3, MRGPRX4, CD200R1, GPR151, RSS, DUSP19, NRG4, VPS13B, OXER1, LCA5, IQGAP1, STAT3, KLF7, KHSRP, EGF, EIF4EBP1, ELN, EPHB2, EPO, F2, FES, FGF1, FN1, FXN, MSTN, GNAT2, GNB1, GRIA1, GRIA2, GRM2, GUCA1B, HCLS1, HLA-DPB1, HLA-DRB1, HMGB1, HRH1, IFNB1, EDA, DPYSL2, CYP19A1, TSPO, ACTN3, AGTR1, AHSG, AIF1, ALOX12, AMD1, AMD1P2, ARL3, ASNS, B2M, CACD, CYBB, CCK, CD38, CD69, CHRM3, CLTA, CRP, CCN2, CTSL, CTSS, CUX1, IGF1, IGSF1, IL2RB, TAC1, SMS, SNRPB, SNRPN, SOAT1, SOX11, SP4, SPP1, STAT1, ACTB, ELOVL4, TCF3, RHO, TFPI, TGFB1, TIMP3, TLR2, TULP1, TULP2, UCHL1, VEGFA, TRPV1, FZD4, S100B, RANGAP1, IL7, MTHFR, ITGAD, KNG1, STMN1, LGALS1, LRP6, MBP, MDK, MIF, CD200, MT1B, MTTP, PTPRF, NOS1, CNTN3, PIK3CA, PIK3CB, PIK3CD, PIK3CG, PLG, MAPK1, PROC, PTEN, LINC02605

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins

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A number sign (#) is used with this entry because of evidence that cone-rod dystrophy-19 (CORD19) is caused by homozygous or compound heterozygous mutation in the TTLL5 gene (612268) on chromosome 14q24.

For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy (CORD), see 120970.

Clinical Features

Sergouniotis et al. (2014) studied 5 patients from 4 families with 'cone-first' retinal dystrophy who had mutations in the TTLL5 gene (see MOLECULAR GENETICS). Three unrelated patients had an almost identical clinical and electrophysiologic phenotype, with central and peripheral cone dysfunction and preservation of rod photoreceptor function. Fundus autofluorescence imaging revealed a high-density concentric perifoveal ring surrounding irregular foveal autofluorescence; outside this ring, normal signal was observed. In contrast, 2 affected brothers had a more severe phenotype with poor vision from the first years of life, severe generalized cone-system dysfunction, and additional significant involvement of rod photoreceptors. Autofluorescence imaging in 1 of the brothers showed hypoautofluorescent patches in the fovea and parafovea, combined with irregular autofluorescence outside the foveal region, suggesting more generalized retinal pigment epithelial dysfunction. Optical coherence tomography (OCT), which was consistent with photoreceptor loss, was confined to the foveal region in the first 3 patients but was observed throughout the scan in the examined brother.

Molecular Genetics

Sergouniotis et al. (2014) performed whole-exome sequencing in 28 patients with 'cone-first' retinal disease and clinical features that were atypical for ABCA4 (601691)-associated retinopathy (see CORD3, 604116). In a gene-based case-control association study using an in-house exome dataset as the control group, they identified 2 patients with homozygous or compound heterozygous mutations in the TTLL5 gene (612268.0001-612268.0003), respectively. Analysis of previously collected exome sequence data from individuals with related phenotypes revealed 2 brothers with early-onset cone-rod dystrophy who were homozygous for a nonsense mutation in TTLL5 (612268.0004). Subsequent testing of a panel of 55 probands with retinal dystrophy identified 1 proband with an adult-onset cone dystrophy phenotype who was homozygous for a TTLL5 missense mutation (612268.0005). Sergouniotis et al. (2014) noted that the retinal phenotype was highly similar in the 3 unrelated patients but that the sib pair had more severe, early-onset disease.