Cone-Rod Dystrophy 8

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

Clinical Features

Khaliq et al. (2000) described a 2-generation, consanguineous Pakistani family with autosomal recessive cone-rod dystrophy. All affected individuals had night blindness, deterioration of central vision, photophobia, epiphora in bright light, and problems with color discrimination. Funduscopy revealed marked macular degeneration and attenuation of retinal vessels; mild pigmentary changes were present in the retinal periphery.

Ismail et al. (2006) reexamined affected members of the Pakistani family with CORD8 previously described by Khaliq et al. (2000). They had suffered loss of color vision, severe photophobia, and epiphora since childhood. Vigorous deterioration in central vision began at age 12, with rapid loss of vision between the ages of 14 and 16 years. Visual acuity among the patients ranged from perception of light, hand movement, and counting fingers to complete blindness. There was a high degree of fundus granularity and marked macular degeneration, with significant levels of attenuated arterioles with the bony corpuscle type of retinal pigment epithelium disturbance. Both photopic and scotopic full-field ERG amplitudes were low, demonstrating the involvement of both cone and rod photoreceptors.

Mapping

In a 2-generation, consanguineous Pakistani family with autosomal recessive CORD, Khaliq et al. (2000) mapped the disease locus, designated CORD8, to chromosome 1q12-q24 (maximum 2-point lod score of 4.22 at theta = 0.0 with marker D1S2635).

Molecular Genetics

Exclusion Studies

By mutation screening in a 2-generation Pakistani family with CORD8, Khaliq et al. (2000) excluded 3 candidate genes, CRABP2 (180231), GNAT2 (139340), and KCNJ10 (602208), as the cause of CORD8. Using additional microsatellite markers in the Pakistani family previously reported by Khaliq et al. (2000), Ismail et al. (2006) excluded mutations in the SEMA4A (607292) and PRPF3 (607301) genes.

In 2 affected members of the 2-generation Pakistani family with CORD mapping to chromosome 1, originally studied by Khaliq et al. (2000), Ansar et al. (2015) analyzed all exons of the ATF6 gene (605537) but did not detect any mutations.