Details of Disease

General Information of Disease (ID: DIS7SAZZ)

• Disease Name: Cone dystrophy
• Synonyms: retinal cone dystrophy; stationary cone dystrophy; progressive cone dystrophy; cone dystrophy
• Definition: An inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision.
• Disease Hierarchy:
  DISEYSYY: Hereditary macular dystrophy
  DIS7SAZZ: Cone dystrophy
• Disease Identifiers:
  MONDO ID: MONDO_0000455
  MESH ID: D000077765
  UMLS CUI: C0730290
  MedGen ID: 676499
  Orphanet ID: 1871
  SNOMED CT ID: 312917007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CNGB3	TT0LJCG	Limited	Genetic Variation	[1]
CNGB3	TT0LJCG	Supportive	Autosomal dominant	[2]
RPGR	TTHBDA9	moderate	Genetic Variation	[3]
ABCA4	TTLB52K	Strong	Genetic Variation	[4]
CNGA3	TTW0QOV	Strong	Genetic Variation	[5]
GUCY2D	TTWNFC2	Strong	Genetic Variation	[6]
TSPAN7	TTMT6VE	Strong	Genetic Variation	[7]
TST	TT51OTS	Strong	Genetic Variation	[8]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
RDH5	DESI4OK	Strong	Genetic Variation	[9]

This Disease Is Related to 23 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
COG4	OT6U94UE	Limited	Genetic Variation	[10]
CNGB3	OTGR3KO5	Supportive	Autosomal dominant	[2]
GNAT2	OTD9Y4UH	Supportive	Autosomal dominant	[11]
PDE6C	OTE7EVWQ	Supportive	Autosomal dominant	[12]
PDE6H	OTMLRB1D	moderate	Genetic Variation	[13]
POMZP3	OTAH2JOK	moderate	Biomarker	[14]
AIPL1	OT4VBD78	Strong	Genetic Variation	[15]
BBS5	OTFWF9N1	Strong	Genetic Variation	[16]
CACNA2D4	OTVYNX7N	Strong	Genetic Variation	[17]
CDHR1	OT1ORXCM	Strong	Genetic Variation	[18]
ERG	OTOTX9VU	Strong	Biomarker	[19]
GNGT2	OTRI3Q10	Strong	Genetic Variation	[20]
GUCA1B	OT85S0J3	Strong	Genetic Variation	[21]
KCNV2	OTLS8OU5	Strong	Genetic Variation	[22]
NYX	OTAGXLYP	Strong	Genetic Variation	[23]
OPN1MW	OTPJ7LX4	Strong	Genetic Variation	[24]
POC1B	OTDIMIRZ	Strong	Biomarker	[25]
PRPH	OT6VUH78	Strong	Genetic Variation	[8]
PRPH2	OTNH2G5H	Strong	Genetic Variation	[7]
RAB28	OTZX5BP6	Strong	CausalMutation	[26]
RLBP1	OTCY4D6B	Strong	Genetic Variation	[27]
RP1L1	OTRKSQWQ	Strong	Genetic Variation	[28]
TTLL5	OTUKOVEM	Strong	Genetic Variation	[29]

References

• [1] Accessory heterozygous mutations in cone photoreceptor CNGA3 exacerbate CNG channel-associated retinopathy.J Clin Invest. 2018 Dec 3;128(12):5663-5675. doi: 10.1172/JCI96098. Epub 2018 Nov 12.
• [2] Progressive cone dystrophy associated with mutation in CNGB3. Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1975-82. doi: 10.1167/iovs.03-0898.
• [3] Improved Diagnosis of Inherited Retinal Dystrophies by High-Fidelity PCR of ORF15 followed by Next-Generation Sequencing.J Mol Diagn. 2016 Nov;18(6):817-824. doi: 10.1016/j.jmoldx.2016.06.007. Epub 2016 Sep 10.
• [4] Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies.PLoS One. 2013 Nov 12;8(11):e78496. doi: 10.1371/journal.pone.0078496. eCollection 2013.
• [5] Diseases associated with mutations in CNGA3: Genotype-phenotype correlation and diagnostic guideline.Prog Mol Biol Transl Sci. 2019;161:1-27. doi: 10.1016/bs.pmbts.2018.10.002. Epub 2018 Nov 23.
• [6] Rapid cohort generation and analysis of disease spectrum of large animal model of cone dystrophy.PLoS One. 2013 Aug 19;8(8):e71363. doi: 10.1371/journal.pone.0071363. eCollection 2013.
• [7] The Late Endosomal Pathway Regulates the Ciliary Targeting of Tetraspanin Protein Peripherin 2.J Neurosci. 2019 May 1;39(18):3376-3393. doi: 10.1523/JNEUROSCI.2811-18.2019. Epub 2019 Feb 28.
• [8] Serine-27-phenylalanine mutation within the peripherin/RDS gene in a family with cone dystrophy.Ophthalmology. 1997 Feb;104(2):299-306. doi: 10.1016/s0161-6420(97)30320-0.
• [9] Young monozygotic twin sisters with fundus albipunctatus and cone dystrophy.Arch Ophthalmol. 2004 Aug;122(8):1203-7. doi: 10.1001/archopht.122.8.1203.
• [10] Mutations in the RPGR gene cause X-linked cone dystrophy.Hum Mol Genet. 2002 Mar 1;11(5):605-11. doi: 10.1093/hmg/11.5.605.
• [11] Cone dystrophy phenotype associated with a frameshift mutation (M280fsX291) in the alpha-subunit of cone specific transducin (GNAT2). Br J Ophthalmol. 2003 Nov;87(11):1317-20. doi: 10.1136/bjo.87.11.1317.
• [12] Homozygosity mapping reveals PDE6C mutations in patients with early-onset cone photoreceptor disorders. Am J Hum Genet. 2009 Aug;85(2):240-7. doi: 10.1016/j.ajhg.2009.06.016. Epub 2009 Jul 16.
• [13] A substitution of G to C in the cone cGMP-phosphodiesterase gamma subunit gene found in a distinctive form of cone dystrophy. Ophthalmology. 2005 Jan;112(1):159-66. doi: 10.1016/j.ophtha.2004.07.011.
• [14] Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.
• [15] AIPL1, A protein linked to blindness, is essential for the stability of enzymes mediating cGMP metabolism in cone photoreceptor cells.Hum Mol Genet. 2014 Feb 15;23(4):1002-12. doi: 10.1093/hmg/ddt496. Epub 2013 Oct 9.
• [16] Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell. 2004 May 14;117(4):541-52. doi: 10.1016/s0092-8674(04)00450-7.
• [17] Mutation in the auxiliary calcium-channel subunit CACNA2D4 causes autosomal recessive cone dystrophy. Am J Hum Genet. 2006 Nov;79(5):973-7. doi: 10.1086/508944. Epub 2006 Sep 27.
• [18] CDHR1 mutations in retinal dystrophies.Sci Rep. 2017 Aug 1;7(1):6992. doi: 10.1038/s41598-017-07117-8.
• [19] Cone dystrophy with "supernormal" rod ERG: psychophysical testing shows comparable rod and cone temporal sensitivity losses with no gain in rod function.Invest Ophthalmol Vis Sci. 2014 Feb 10;55(2):832-40. doi: 10.1167/iovs.13-12919.
• [20] Exon screening of the genes encoding the beta- and gamma-subunits of cone transducin in patients with inherited retinal disease.Mol Vis. 1998 Sep 17;4:16.
• [21] Mutation screening of the GUCA1B gene in patients with autosomal dominant cone and cone rod dystrophy.Ophthalmic Genet. 2011 Sep;32(3):151-5. doi: 10.3109/13816810.2011.559650. Epub 2011 Mar 15.
• [22] The importance of electrophysiology in revealing a complete homozygous deletion of KCNV2.J AAPOS. 2013 Dec;17(6):641-3. doi: 10.1016/j.jaapos.2013.08.006. Epub 2013 Nov 7.
• [23] Localization of CSNBX (CSNB4) between the retinitis pigmentosa loci RP2 and RP3 on proximal Xp.Invest Ophthalmol Vis Sci. 1997 Dec;38(13):2750-5.
• [24] De novo intrachromosomal gene conversion from OPN1MW to OPN1LW in the male germline results in Blue Cone Monochromacy.Sci Rep. 2016 Jun 24;6:28253. doi: 10.1038/srep28253.
• [25] Phenotypical Characteristics of POC1B-Associated Retinopathy in Japanese Cohort: Cone Dystrophy With Normal Funduscopic Appearance.Invest Ophthalmol Vis Sci. 2019 Aug 1;60(10):3432-3446. doi: 10.1167/iovs.19-26650.
• [26] New mutations in the RAB28 gene in 2 Spanish families with cone-rod dystrophy. JAMA Ophthalmol. 2015 Feb;133(2):133-9. doi: 10.1001/jamaophthalmol.2014.4266.
• [27] A homozygous frameshift mutation in LRAT causes retinitis punctata albescens.Ophthalmology. 2012 Sep;119(9):1899-906. doi: 10.1016/j.ophtha.2012.02.037. Epub 2012 May 3.
• [28] Cone dystrophy in patient with homozygous RP1L1 mutation.Biomed Res Int. 2015;2015:545243. doi: 10.1155/2015/545243. Epub 2015 Jan 29.
• [29] Novel splice-site mutation in TTLL5 causes cone dystrophy in a consanguineous family.Mol Vis. 2017 Mar 18;23:131-139. eCollection 2017.