Skip to main content
PMC home page
Journal of Medical Genetics logoLink to Journal of Medical Genetics
. 2000 Jul;37(7):481–488. doi: 10.1136/jmg.37.7.481

The genetics of childhood cataract

P Francis 1, V Berry 1, S Bhattacharya 1, A Moore 1
PMCID: PMC1734631  PMID: 10882749

Abstract

Human congenital cataract has a diverse aetiology. In the proportion of cases where the cause is genetic, the disease shows wide phenotypic and genetic heterogeneity. Over the past few years, much research has been devoted to mapping the genes that underlie the disorder. This has been helped by the extensive array of naturally occurring and genetically engineered mouse cataract models and the abundance of human candidate genes. Most progress to date has been in the identification of genetic mutations causing autosomal dominant congenital cataract where eight genes have been implicated in cataractogenesis. Overall there is good correlation between the genetic mutations so far identified and the resulting lens phenotype but it is clear that mutations at more that one locus may give rise to similar forms of cataract.
The identification of genes causing inherited forms of cataract will improve our understanding of the mechanisms underlying cataractogenesis in childhood and provide further insights into normal lens development and physiology. Perhaps more importantly, it is likely that some of the genes causing early onset cataract will be implicated in age related cataract which remains the commonest cause of blindness in the world.


Keywords: cataract; congenital; genetics; phenotype

Full Text

The Full Text of this article is available as a PDF (178.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armitage M. M., Kivlin J. D., Ferrell R. E. A progressive early onset cataract gene maps to human chromosome 17q24. Nat Genet. 1995 Jan;9(1):37–40. doi: 10.1038/ng0195-37. [DOI] [PubMed] [Google Scholar]
  2. Berry V., Francis P., Kaushal S., Moore A., Bhattacharya S. Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q. Nat Genet. 2000 May;25(1):15–17. doi: 10.1038/75538. [DOI] [PubMed] [Google Scholar]
  3. Berry V., Ionides A. C., Moore A. T., Plant C., Bhattacharya S. S., Shiels A. A locus for autosomal dominant anterior polar cataract on chromosome 17p. Hum Mol Genet. 1996 Mar;5(3):415–419. doi: 10.1093/hmg/5.3.415. [DOI] [PubMed] [Google Scholar]
  4. Bodker F. S., Lavery M. A., Mitchell T. N., Lovrien E. W., Maumenee I. H. Microphthalmos in the presumed homozygous offspring of a first cousin marriage and linkage analysis of a locus in a family with autosomal dominant cerulean congenital cataracts. Am J Med Genet. 1990 Sep;37(1):54–59. doi: 10.1002/ajmg.1320370113. [DOI] [PubMed] [Google Scholar]
  5. Bouzas A. G. Anterior polar congenital cataract and corneal astigmatism. J Pediatr Ophthalmol Strabismus. 1992 Jul-Aug;29(4):210–212. doi: 10.3928/0191-3913-19920701-05. [DOI] [PubMed] [Google Scholar]
  6. Brakenhoff R. H., Henskens H. A., van Rossum M. W., Lubsen N. H., Schoenmakers J. G. Activation of the gamma E-crystallin pseudogene in the human hereditary Coppock-like cataract. Hum Mol Genet. 1994 Feb;3(2):279–283. doi: 10.1093/hmg/3.2.279. [DOI] [PubMed] [Google Scholar]
  7. Cartier M., Breitman M. L., Tsui L. C. A frameshift mutation in the gamma E-crystallin gene of the Elo mouse. Nat Genet. 1992 Sep;2(1):42–45. doi: 10.1038/ng0992-42. [DOI] [PubMed] [Google Scholar]
  8. Chambers C., Russell P. Deletion mutation in an eye lens beta-crystallin. An animal model for inherited cataracts. J Biol Chem. 1991 Apr 15;266(11):6742–6746. [PubMed] [Google Scholar]
  9. Chang B., Hawes N. L., Roderick T. H., Smith R. S., Heckenlively J. R., Horwitz J., Davisson M. T. Identification of a missense mutation in the alphaA-crystallin gene of the lop18 mouse. Mol Vis. 1999 Sep 10;5:21–21. [PubMed] [Google Scholar]
  10. Clementi M., Rossetti A., Pesenti P., Tenconi R. Microphthalmia-congenital anterior polar cataract. An autosomal dominant syndrome. Ophthalmic Paediatr Genet. 1985 Dec;6(3):189–191. doi: 10.3109/13816818509087640. [DOI] [PubMed] [Google Scholar]
  11. Donahue R. P., Bias W. B., Renwick J. H., McKusick V. A. Probable assignment of the Duffy blood group locus to chromosome 1 in man. Proc Natl Acad Sci U S A. 1968 Nov;61(3):949–955. doi: 10.1073/pnas.61.3.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Eiberg H., Lund A. M., Warburg M., Rosenberg T. Assignment of congenital cataract Volkmann type (CCV) to chromosome 1p36. Hum Genet. 1995 Jul;96(1):33–38. doi: 10.1007/BF00214183. [DOI] [PubMed] [Google Scholar]
  13. Eiberg H., Marner E., Rosenberg T., Mohr J. Marner's cataract (CAM) assigned to chromosome 16: linkage to haptoglobin. Clin Genet. 1988 Oct;34(4):272–275. doi: 10.1111/j.1399-0004.1988.tb02875.x. [DOI] [PubMed] [Google Scholar]
  14. Francis P. J., Berry V., Moore A. T., Bhattacharya S. Lens biology: development and human cataractogenesis. Trends Genet. 1999 May;15(5):191–196. doi: 10.1016/s0168-9525(99)01738-2. [DOI] [PubMed] [Google Scholar]
  15. François J. Genetics of cataract. Ophthalmologica. 1982;184(2):61–71. doi: 10.1159/000309186. [DOI] [PubMed] [Google Scholar]
  16. Gill D., Klose R., Munier F. L., McFadden M., Priston M., Billingsley G., Ducrey N., Schorderet D. F., Héon E. Genetic heterogeneity of the Coppock-like cataract: a mutation in CRYBB2 on chromosome 22q11.2. Invest Ophthalmol Vis Sci. 2000 Jan;41(1):159–165. [PubMed] [Google Scholar]
  17. Gong X., Li E., Klier G., Huang Q., Wu Y., Lei H., Kumar N. M., Horwitz J., Gilula N. B. Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell. 1997 Dec 12;91(6):833–843. doi: 10.1016/s0092-8674(00)80471-7. [DOI] [PubMed] [Google Scholar]
  18. Goodenough D. A., Goliger J. A., Paul D. L. Connexins, connexons, and intercellular communication. Annu Rev Biochem. 1996;65:475–502. doi: 10.1146/annurev.bi.65.070196.002355. [DOI] [PubMed] [Google Scholar]
  19. Graw J. Cataract mutations and lens development. Prog Retin Eye Res. 1999 Mar;18(2):235–267. doi: 10.1016/s1350-9462(98)00018-4. [DOI] [PubMed] [Google Scholar]
  20. Graw J. Cataract mutations as a tool for developmental geneticists. Ophthalmic Res. 1996;28 (Suppl 1):8–18. doi: 10.1159/000267936. [DOI] [PubMed] [Google Scholar]
  21. Graw J., Jung M., Löster J., Klopp N., Soewarto D., Fella C., Fuchs H., Reis A., Wolf E., Balling R. Mutation in the betaA3/A1-crystallin encoding gene Cryba1 causes a dominant cataract in the mouse. Genomics. 1999 Nov 15;62(1):67–73. doi: 10.1006/geno.1999.5974. [DOI] [PubMed] [Google Scholar]
  22. Héon E., Priston M., Schorderet D. F., Billingsley G. D., Girard P. O., Lubsen N., Munier F. L. The gamma-crystallins and human cataracts: a puzzle made clearer. Am J Hum Genet. 1999 Nov;65(5):1261–1267. doi: 10.1086/302619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ionides A. C., Berry V., Mackay D. S., Moore A. T., Bhattacharya S. S., Shiels A. A locus for autosomal dominant posterior polar cataract on chromosome 1p. Hum Mol Genet. 1997 Jan;6(1):47–51. doi: 10.1093/hmg/6.1.47. [DOI] [PubMed] [Google Scholar]
  24. Ionides A., Francis P., Berry V., Mackay D., Bhattacharya S., Shiels A., Moore A. Clinical and genetic heterogeneity in autosomal dominant cataract. Br J Ophthalmol. 1999 Jul;83(7):802–808. doi: 10.1136/bjo.83.7.802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Janssen E. A., Kemp S., Hensels G. W., Sie O. G., de Die-Smulders C. E., Hoogendijk J. E., de Visser M., Bolhuis P. A. Connexin32 gene mutations in X-linked dominant Charcot-Marie-Tooth disease (CMTX1). Hum Genet. 1997 Apr;99(4):501–505. doi: 10.1007/s004390050396. [DOI] [PubMed] [Google Scholar]
  26. Kannabiran C., Rogan P. K., Olmos L., Basti S., Rao G. N., Kaiser-Kupfer M., Hejtmancik J. F. Autosomal dominant zonular cataract with sutural opacities is associated with a splice mutation in the betaA3/A1-crystallin gene. Mol Vis. 1998 Oct 23;4:21–21. [PubMed] [Google Scholar]
  27. Kelsell D. P., Dunlop J., Stevens H. P., Lench N. J., Liang J. N., Parry G., Mueller R. F., Leigh I. M. Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature. 1997 May 1;387(6628):80–83. doi: 10.1038/387080a0. [DOI] [PubMed] [Google Scholar]
  28. Klopp N., Favor J., Löster J., Lutz R. B., Neuhäuser-Klaus A., Prescott A., Pretsch W., Quinlan R. A., Sandilands A., Vrensen G. F. Three murine cataract mutants (Cat2) are defective in different gamma-crystallin genes. Genomics. 1998 Sep 1;52(2):152–158. doi: 10.1006/geno.1998.5417. [DOI] [PubMed] [Google Scholar]
  29. Krill A. E., Woodbury G., Bowman J. E. X-chromosomal-linked sutural cataracts. Am J Ophthalmol. 1969 Nov;68(5):867–872. doi: 10.1016/0002-9394(69)94582-6. [DOI] [PubMed] [Google Scholar]
  30. Lambert S. R., Drack A. V. Infantile cataracts. Surv Ophthalmol. 1996 May-Jun;40(6):427–458. doi: 10.1016/s0039-6257(96)82011-x. [DOI] [PubMed] [Google Scholar]
  31. Litt M., Carrero-Valenzuela R., LaMorticella D. M., Schultz D. W., Mitchell T. N., Kramer P., Maumenee I. H. Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta-crystallin gene CRYBB2. Hum Mol Genet. 1997 May;6(5):665–668. doi: 10.1093/hmg/6.5.665. [DOI] [PubMed] [Google Scholar]
  32. Litt M., Kramer P., LaMorticella D. M., Murphey W., Lovrien E. W., Weleber R. G. Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Hum Mol Genet. 1998 Mar;7(3):471–474. doi: 10.1093/hmg/7.3.471. [DOI] [PubMed] [Google Scholar]
  33. Lubsen N. H., Aarts H. J., Schoenmakers J. G. The evolution of lenticular proteins: the beta- and gamma-crystallin super gene family. Prog Biophys Mol Biol. 1988;51(1):47–76. doi: 10.1016/0079-6107(88)90010-7. [DOI] [PubMed] [Google Scholar]
  34. Mackay D., Ionides A., Kibar Z., Rouleau G., Berry V., Moore A., Shiels A., Bhattacharya S. Connexin46 mutations in autosomal dominant congenital cataract. Am J Hum Genet. 1999 May;64(5):1357–1364. doi: 10.1086/302383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Marner E., Rosenberg T., Eiberg H. Autosomal dominant congenital cataract. Morphology and genetic mapping. Acta Ophthalmol (Copenh) 1989 Apr;67(2):151–158. doi: 10.1111/j.1755-3768.1989.tb00745.x. [DOI] [PubMed] [Google Scholar]
  36. Mathew S., Chaudhuri A., Murty V. V., Pogo A. O. Confirmation of Duffy blood group antigen locus (FY) at 1q22-->q23 by fluorescence in situ hybridization. Cytogenet Cell Genet. 1994;67(1):68–68. doi: 10.1159/000133801. [DOI] [PubMed] [Google Scholar]
  37. Miller B. A., Jaafar M. S., Capo H. Chromosome 14-terminal deletion and cataracts. Arch Ophthalmol. 1992 Aug;110(8):1053–1053. doi: 10.1001/archopht.1992.01080200033015. [DOI] [PubMed] [Google Scholar]
  38. Moross T., Vaithilingam S. S., Styles S., Gardner H. A. Autosomal dominant anterior polar cataracts associated with a familial 2;14 translocation. J Med Genet. 1984 Feb;21(1):52–53. doi: 10.1136/jmg.21.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ogata H., Okubo Y., Akabane T. Phenotype i associated with congenital cataract in Japanese. Transfusion. 1979 Mar-Apr;19(2):166–168. doi: 10.1046/j.1537-2995.1979.19279160286.x. [DOI] [PubMed] [Google Scholar]
  40. Parks M. M., Johnson D. A., Reed G. W. Long-term visual results and complications in children with aphakia. A function of cataract type. Ophthalmology. 1993 Jun;100(6):826–841. doi: 10.1016/s0161-6420(93)31566-6. [DOI] [PubMed] [Google Scholar]
  41. Piatigorsky J. Gene sharing in lens and cornea: facts and implications. Prog Retin Eye Res. 1998 Apr;17(2):145–174. doi: 10.1016/s1350-9462(97)00004-9. [DOI] [PubMed] [Google Scholar]
  42. RENWICK J. H., LAWLER S. D. PROBABLE LINKAGE BETWEEN A CONGENITAL CATARACT LOCUS AND THE DUFFY BLOOD GROUP LOCUS. Ann Hum Genet. 1963 Aug;27:67–84. doi: 10.1111/j.1469-1809.1963.tb00782.x. [DOI] [PubMed] [Google Scholar]
  43. Rogaev E. I., Rogaeva E. A., Korovaitseva G. I., Farrer L. A., Petrin A. N., Keryanov S. A., Turaeva S., Chumakov I., St George-Hyslop P., Ginter E. K. Linkage of polymorphic congenital cataract to the gamma-crystallin gene locus on human chromosome 2q33-35. Hum Mol Genet. 1996 May;5(5):699–703. doi: 10.1093/hmg/5.5.699. [DOI] [PubMed] [Google Scholar]
  44. Scott M. H., Hejtmancik J. F., Wozencraft L. A., Reuter L. M., Parks M. M., Kaiser-Kupfer M. I. Autosomal dominant congenital cataract. Interocular phenotypic variability. Ophthalmology. 1994 May;101(5):866–871. doi: 10.1016/s0161-6420(94)31246-2. [DOI] [PubMed] [Google Scholar]
  45. Semina E. V., Ferrell R. E., Mintz-Hittner H. A., Bitoun P., Alward W. L., Reiter R. S., Funkhauser C., Daack-Hirsch S., Murray J. C. A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. Nat Genet. 1998 Jun;19(2):167–170. doi: 10.1038/527. [DOI] [PubMed] [Google Scholar]
  46. Semina E. V., Reiter R. S., Murray J. C. Isolation of a new homeobox gene belonging to the Pitx/Rieg family: expression during lens development and mapping to the aphakia region on mouse chromosome 19. Hum Mol Genet. 1997 Nov;6(12):2109–2116. doi: 10.1093/hmg/6.12.2109. [DOI] [PubMed] [Google Scholar]
  47. Shiels A., Bassnett S. Mutations in the founder of the MIP gene family underlie cataract development in the mouse. Nat Genet. 1996 Feb;12(2):212–215. doi: 10.1038/ng0296-212. [DOI] [PubMed] [Google Scholar]
  48. Shiels A., Mackay D., Ionides A., Berry V., Moore A., Bhattacharya S. A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q. Am J Hum Genet. 1998 Mar;62(3):526–532. doi: 10.1086/301762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Stambolian D., Lewis R. A., Buetow K., Bond A., Nussbaum R. Nance-Horan syndrome: localization within the region Xp21.1-Xp22.3 by linkage analysis. Am J Hum Genet. 1990 Jul;47(1):13–19. [PMC free article] [PubMed] [Google Scholar]
  50. Steele E. C., Jr, Lyon M. F., Favor J., Guillot P. V., Boyd Y., Church R. L. A mutation in the connexin 50 (Cx50) gene is a candidate for the No2 mouse cataract. Curr Eye Res. 1998 Sep;17(9):883–889. doi: 10.1076/ceyr.17.9.883.5144. [DOI] [PubMed] [Google Scholar]
  51. Stephan D. A., Gillanders E., Vanderveen D., Freas-Lutz D., Wistow G., Baxevanis A. D., Robbins C. M., VanAuken A., Quesenberry M. I., Bailey-Wilson J. Progressive juvenile-onset punctate cataracts caused by mutation of the gammaD-crystallin gene. Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1008–1012. doi: 10.1073/pnas.96.3.1008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Taylor D. The Doyne Lecture. Congenital cataract: the history, the nature and the practice. Eye (Lond) 1998;12(Pt 1):9–36. doi: 10.1038/eye.1998.5. [DOI] [PubMed] [Google Scholar]
  53. Warburg M. X-linked cataract and X-linked microphthalmos: how many deletion families? Am J Med Genet. 1989 Nov;34(3):451–453. doi: 10.1002/ajmg.1320340324. [DOI] [PubMed] [Google Scholar]
  54. Yokoyama Y., Narahara K., Tsuji K., Ninomiya S., Seino Y. Autosomal dominant congenital cataract and microphthalmia associated with a familial t(2;16) translocation. Hum Genet. 1992 Sep-Oct;90(1-2):177–178. doi: 10.1007/BF00210770. [DOI] [PubMed] [Google Scholar]
  55. Zelante L., Gasparini P., Estivill X., Melchionda S., D'Agruma L., Govea N., Milá M., Monica M. D., Lutfi J., Shohat M. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet. 1997 Sep;6(9):1605–1609. doi: 10.1093/hmg/6.9.1605. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Medical Genetics are provided here courtesy of BMJ Publishing Group

RESOURCES