Scientific Mutation Database
Mutations of the Cone Rod Homeobox Gene

Recent update from: 16.06.2005


Phenotype Mutation Basechange Nucleotide Exon Restriction Site Classification
& Remarks
Mutation Database OMIM Reference
Microarray indicates unpublished mutations Italics font indicates mutations spotted on a mutation detection microarray.



nd = not determined




Sequence

0 0
The sequence data are adjusted to a sequence given in a WORD file which can be downloaded here. Nucleotides are counted from the translation start site as used in most of the recent publications of CRX mutations.




LCA 21insG CCG GGG CCC>CCG GGG GCC C 0021 1
Mutation deletes homeodomain, WSP motif and OTX tail
Father of patient carries the mutation, but is not affected
"Haploinsufficiency of CRX is not sufficient to cause a retinal disorder"
Null mutation
goto HMGD
(14)
(1)
Rare variant IVS1+12c/t gtcgt>gccgt 0100 IVS1



(18)
Polymorphism IVS1+2t/c A gtga>A gcga 0100 IVS1



(12)
Polymorphism IVS1-13c/g cccat/cgcat 0101 IVS1



(22)
Polymorphism IVS1-65a/t ccagc>cctgc 0101 IVS1



(16)
CORD2 Arg 41 Trp CGG>TGG 0121 2
Protein localized in nucleus
goto HMGD 602225-0005 (18)
(5)
isolate RP Arg 41 Gln CGG>CAG 0122 2

007-051
goto HMGD 602225-0006 (11)
ADRP Arg 41 Gln CGG>CAG 0122 2

goto HMGD 602225-0006 (17)
CORD2 Arg 41 Gln CGG>CAG 0122 2

goto HMGD
(18)
(21)
LCA Ala 56 Thr GCA>ACA 0166 2

goto HGMD
(8)
Microarray Val 66 Ile GTC>ATC 0196 2






CORD2 Glu 80 Lys GAG>AAG 0238 2 -HinfI Southern Finland
Protein localized in nucleus
goto HGMD
(13)
CORD2 Glu 80 Ala GAG>GCG 0239 2 -DdeI, -HinfI
goto HGMD 602225-0001 (2)
(17)
(15)
Polymorphism IVS2-15g/a ccgct>ccact 0253 IVS2

182-007


(17)
Polymorphism IVS2-18t/a tctcc>tcacc 0253 IVS2

289-026


(17)
(12)
LCA Arg 90 Trp
0268 3
Nuclear localization is impaired
goto HGMD 602225-0007 (19)
LCA? Ala 112 Val GCC>GTC 0335 3



(22)
CORD2 351ins C GCC AAG>GCC CAA G 0351 3



(2)
ADRP Gly 122 Asp GGC>GAC 0365 3

goto HGMD
(15)
Microarray Tyr 142 Cys TAC>TGC 0425 1






ADRP 436del12bp CCT CTG CCC GGC CCC TCA>CCT ___ ___ ___ ___ TCA 0436 3

goto HGMD
(17)
(20)
Microarray 444insC TAC>TGC 0444 1






CORD2 Ala 158 Thr GCC>ACC 0472 3

goto HGMD
(18)
(8)
CORD2 502delG TCA GAG>TCA _AG 0505 3

goto HGMD 602225-0002 (2)
(6)
LCA 503delAG TCA GAG TCC>TCA G__ TCC 0501 3

goto HGMD 602225-0003 (3)
(8)
(6)
LCA 505delT GAG TCC>GAG _CC 0505 3



(10)
Microarray 519delG GAG GCG>GA_ GCG 0519 3



(9)
LCA 529delG CGG GCT >CGG _CT 0529 3



(7)
Microarray 541delG GAG GCG>GA_ GCG 0541 3



(22)
Polymorphism Gly 183 Gly GGG / GGA 0549 05



(17)
LCA / CRD 571delT TAT>_AT 0571 3
de novo


(12)
CORD2 585insC TAC GCC>TAC CGC C 0585 3

goto HGMD
(17)
(21)
CORD2 587delCCCC TAC GCC CCG GCC>TAC G__ __G GCC 0587 3

goto HGMD
(18)
(15)
Polymorphism Ser 199 Ser TCC / TCT 0597 3



(17)
CORD2 613delC TCC CCC TCC>T_C CCC TCC 0613 3





(4)
LCA 649delG AGC GGC>AGC _GC 0649 3

goto HGMD 602225-0004 (3)
(6)
(8)
LCA 705delC CTT AGC CCC CTC>CTT AG_ CCC CTC 0705 3
Heterozygous
de novo


(1)
(14)
CORD2 Val 242 Met GTG>ATG 0724 3

goto HGMD
(18)
(11)
Microarray 742ins23bp dup720-742 GCC CAG>GCC CTC CGT GGG ACC TTC CCT GGC CCC AG 0742 3





Microarray 753delC ACC TCC>AC_ TCC 0753 3





LCA / CRD 786delC TAC AGC CCC GTG>TAC AG_ CCC GTG 0786 3



(12)
Microarray Thr 273 Met ACG>ATG 0818 3
Asper reports this mutation as T273L




References

  1. Dharmaraj,S.R., Silva,E.R., Pina,A.L., Li,Y.Y., Yang,J.M., Carter,C.R., Loyer,M.K., El Hilali,H.K., Traboulsi,E.K., Sundin,O.K., Zhu,D.K., Koenekoop,R.K., and Maumenee,I.H. Mutational analysis and clinical correlation in leber congenital amaurosis. 2000; Ophthalm.Genet. 21: 135-150.
    Link Goto Top
  2. Freund,C.L., Gregory Evans,C.Y., Furukawa,T., Papaioannou,M., Looser,J., Ploder,L., Bellingham,J., Ng,D., Herbrick,J.A., Duncan,A., Scherer,S.W., Tsui,L.C., Loutradis Anagnostou,A., Jacobson,S.G., Cepko,C.L., Bhattacharya,S.S., and McInnes,R.R. Cone-rod dystrophy due to mutations in a novel photoreceptor- specific homeobox gene (CRX) essential for maintenance of the photoreceptor. 1997; Cell. 91: 543-553.
    Link Goto Top
  3. Freund,C.L., Wang,Q.L., Chen,S., Muskat,B.L., Wiles,C.D., Sheffield,V.C., Jacobson,S.G., McInnes,R.R., Zack,D.J., and Stone,E.M. De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis. 1998; Nat.Genet. 18: 311-312.
    Link Goto Top
  4. Itabashi,T., Wada,Y., Sato,H., Kawamura,M., Shiono,T., and Tamai,M. Novel 615delC mutation in the CRX gene in a Japanese family with cone-rod dystrophy. 2004; Am J Ophthalmol. 138: 876-877. Link Goto Top
  5. Itabashi,T., Wada,Y., Sato,H., Kunikata,H., Kawamura,M., and Tamai,M. Ocular findings in a Japanese family with an Arg41Trp mutation of the CRX gene. 2003; Graefes Arch.Clin.Exp.Ophthalmol. 241: 535-540. Link Goto Top
  6. Jacobson,S.G., Cideciyan,A.V., Huang,Y., Freund,C.L., and McInnes,R.R. Disease Phenotype Of A Retinal Degeneration Due To A Truncation Mutation In The CRX Gene. 1998; Invest.Ophthalmol.Vis.Sci. 39: S966 Goto Top
  7. Koenekoop,R.K., Loyer,M., Dembinska,O., and Beneish,R. Visual improvement in Leber congenital amaurosis and the CRX genotype. 2002; Ophthalmic Genet. 23: 49-59. Link Goto Top
  8. Lotery,A.J., Namperumalsamy,P., Jacobson,S.G., Weleber,R.G., Fishman,G.A., Musarella,M.A., Hoyt,C.S., Heon,E., Levin,A., Jan,J., Lam,B., Carr,R.E., Franklin,A., Radha,S., Andorf,J.L., Sheffield,V.C., and Stone,E.M. Mutation analysis of 3 genes in patients with Leber congenital amaurosis. 2000; Arch.Ophthalmol. 118: 538-543.
    Link Goto Top
  9. Nakamura,M., Ito,S., and Miyake,Y. Novel de novo mutation in CRX gene in a Japanese patient with leber congenital amaurosis. 2002; Am.J.Ophthalmol. 134: 465-467. Link Goto Top
  10. Perrault,I., Hanein,S., Gerber,S., Barbet,F., Dufier,J.L., Munnich,A., Rozet,J.M., and Kaplan,J. Evidence of autosomal dominant Leber congenital amaurosis (LCA) underlain by a CRX heterozygous null allele. 2003; J.Med.Genet. 40: e90 Link Goto Top
  11. Rivolta,C., Berson,E.L., and Dryja,T.P. Dominant Leber congenital amaurosis, cone-rod degeneration, and retinitis pigmentosa caused by mutant versions of the transcription factor CRX. 2001; Hum.Mutat. 18: 488-498.
    Link Goto Top
  12. Rivolta,C., Peck,N.E., Fulton,A.B., Fishman,G.A., Berson,E.L., and Dryja,T.P. Novel frameshift mutations in CRX associated with Leber congenital amaurosis. 2001; Hum.Mutat. 18: 550-551.
    Link Goto Top
  13. Sankila,E.M., Joensuu,T.H., Hamalainen,R.H., Raitanen,N., Valle,O., Ignatius,J., and Cormand,B. A CRX mutation in a Finnish family with dominant cone-rod retinal dystrophy. 2000; Hum Mutat. 16: 94 Link Goto Top
  14. Silva,E., Yang,J.M., Li,Y., Dharmaraj,S., Sundin,O.H., and Maumenee,I.H. A CRX null mutation is associated with both Leber congenital amaurosis and a normal ocular phenotype. 2000; Invest.Ophthalmol.Vis.Sci. 41: 2076-2079.
    Link Goto Top
  15. Sohocki,M.M., Daiger,S.P., Bowne,S.J., Rodriquez,J.A., Northrup,H., Heckenlively,J.R., Birch,D.G., Mintz-Hittner,H., Ruiz,R.S., Lewis,R.A., Saperstein,D.A., and Sullivan,L.S. Prevalence of mutations causing retinitis pigmentosa and other inherited retinopathies. 2001; Hum.Mutat. 17: 42-51.
    Link Goto Top
  16. Sohocki,M.M., Malone,K.A., Sullivan,L.S., and Daiger,S.P. Identification and mapping of novel candidate genes for inherited retinal disorders. 1998; Am.J.Hum.Genet. 63: A386 Goto Top
  17. Sohocki,M.M., Sullivan,L.S., Mintz-Hittner,H.A., Birch,D., Heckenlively,J.R., Freund,C.L., McInnes,R.R., and Daiger,S.P. A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene. 1998; Am.J.Hum.Genet. 63: 1307-1315.
    Link Goto Top
  18. Swain,P.K., Chen,S., Wang,Q.L., Affatigato,L.M., Coats,C.L., Brady,K.D., Fishman,G.A., Jacobson,S.G., Swaroop,A., Stone,E., Sieving,P.A., and Zack,D.J. Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration. 1997; Neuron. 19: 1329-1336.
    Link Goto Top
  19. Swaroop,A., Wang,Q.L., Wu,W., Cook,J., Coats,C., Xu,S., Chen,S., Zack,D.J., and Sieving,P.A. Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function. 1999; Hum.Mol.Genet. 8: 299-305.
    Link Goto Top
  20. Tzekov,R.T., Liu,Y., Sohocki,M.M., Zack,D.J., Daiger,S.P., Heckenlively,J.R., and Birch,D.G. Autosomal dominant retinal degeneration and bone loss in patients with a 12-bp deletion in the CRX gene. 2001; Invest.Ophthalmol.Vis.Sci. 42: 1319-1327.
    Link Goto Top
  21. Tzekov,R.T., Sohocki,M.M., Daiger,S.P., and Birch,D.G. Visual phenotype in patients with Arg41Gln and ala196+1bp mutations in the CRX gene. 2000; Ophthalmic Genet. 21: 89-99. Link Goto Top
  22. Zhang,Q.J., Xiao,X.S., Li,S.Q., Zhang,F.S., Guo,X.M., Jia,X.Y., Shen,H.X., Li,J.Z., Li,W., and Yang,L.P. Family collection and candidate gene analysis of genetic eye diseases. 2001; Invest.Ophthalmol.Vis.Sci. 42: S646 Goto Top

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This site is maintained and edited by
Dr. rer. medic. Markus Preising, Dipl.Biol.
Molecular Genetics Laboratory
Department of Paediatric Ophthalmology, Strabismology and Ophthalmogenetics
University of Regensburg
Head: Prof. Dr. med. Birgit Lorenz