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Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts

By E. Nandrot, Christine Slingsby, Ajit K. Basak, M. Cherif Chefchaouni, B. Benazzouz, Y. Hajaji, S. Boutayeb, O. Gribouval, L. Arbogast, A. Berraho, M. Abitbol and L. Hilal


Congenital cataracts are a major cause of bilateral visual impairment in childhood. We mapped the gene responsible for autosomal congenital cerulean cataracts to chromosome 2q33-35 in a four generation family of Moroccan descent. The maximum lod score (7.19 at recombination fraction theta=0) was obtained for marker D2S2208 near the g-crystallin gene (CRYG) cluster. Sequencing of the coding regions of the CRYGA, B, C, and D genes showed the presence of a heterozygous C>A transversion in exon 2 of CRYGD that is associated with cataracts in this family. This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterise this protein. We show that although the x ray crystallography modelling does not indicate any change of the backbone conformation, the mutation affects a region of the Greek key motif that is important for determining the topology of this protein fold. Our data suggest strongly that the proline to threonine substitution may alter the protein folding or decrease the thermodynamic stability or solubility of the protein. Furthermore, this is the first report of a mutation in this gene resulting in autosomal dominant congenital cerulean cataracts

Topics: bcs
Publisher: BMJ Publishing Group
Year: 2003
OAI identifier:

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  4. (1998). A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant “zonular pulverulent” cataract, on chromosome 1q. doi
  5. A nonsense mutation in CRYBB1 associated with autosomal dominant cataract linked to human chromosome 22q. doi
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  7. (1998). A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD. doi
  8. A program to check the stereochemical quality of protein structures. doi
  9. (1995). A progressive early onset cataract gene maps to human chromosome 17q24. doi
  10. A second gene for cerulean cataracts maps to the beta crystallin region on chromosome 22. Genomics doi
  11. A superfamily in the mammalian eye lens: the beta/gamma-crystallins. Mol Biol Rep doi
  12. Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. doi
  13. (1998). Anterior polar cataract: clinical spectrum and genetic linkage in a single family. Eye doi
  14. (1986). Assignment of the human gamma-crystallin gene cluster (CRYG) to the long arm of chromosome 2, region q33-36. Hum Genet doi
  15. Autosomal dominant cerulean cataract is doi
  16. (1994). Autosomal dominant congenital cataract. Interocular phenotypic variability. doi
  17. Autosomal-dominant congenital cataract associated with a deletion mutation in the human beaded filament protein gene BFSP2. doi
  18. (1997). Basak, et al associated with a chain termination mutation in the human beta-crystallin gene CRYBB2. Hum Mol Genet
  19. (1997). Basak, et al www.jmedgenet.comassociated with a chain termination mutation in the human beta-crystallin gene CRYBB2. Hum Mol Genet
  20. Burger JA unique form of autosomal dominant cataract explained by gene conversion between beta-crystallin B2 and its pseudogene. doi
  21. Cataract mutations and lens development. Prog Retin Eye Res
  22. (1996). Cataract mutations as a tool for developmental geneticists. Ophthalmic Res doi
  23. Conformational change and destabilization of cataract gammaC-crystallin T5P mutant. FEBS Lett 2002;513:213-16. A CRYGD mutation in cerulean cataracts 267 doi
  24. Congenital cataracts: gene mapping. doi
  25. (1999). Connexin46 mutations in autosomal dominant congenital cataract. doi
  26. Crygf(Rop): the first mutation in the Crygf gene causing a unique radial lens opacity.
  27. Crystal cataracts: human genetic cataract caused by protein crystallization. doi
  28. Crystallography & NMR system: a new software suite for macromolecular structure determination. doi
  29. de Angelis MH. Characterization of a new, dominant V124E mutation in the mouse alphaA-crystallin-encoding gene. Invest Ophthalmol Vis Sci doi
  30. Drack AV. Infantile cataracts. doi
  31. Easy calculations of lod scores and genetic risks on small computers.
  32. (1997). Electron density map interpretation. Methods Enzymol
  33. Empirical predictions of protein conformation. doi
  34. Evidence of clinical and genetic heterogeneity in autosomal dominant congenital cerulean cataracts. doi
  35. Faster sequential genetic linkage computations.
  36. Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. Hum doi
  37. (2000). Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11 (CZP3) and a novel mutation in connexin 46 (GJA3). Hum Genet doi
  38. (1998). Gene localization for aculeiform cataract, on chromosome 2q33-35. doi
  39. Genetic heterogeneity of the Coppock-like cataract: a mutation in
  40. (1998). Genetical investigations in congenital cataract cases.
  41. High-resolution x-ray crystal structures of human gD crystallin (1.25Å) and the R58H mutant (1.15Å) associated with aculeiform cataract. doi
  42. High-resolution x-ray crystal structures of human γD crystallin (1.25Å) and the R58H mutant (1.15Å) associated with aculeiform cataract. doi
  43. Human gamma-crystallin genes. A gene family on its way to extinction.
  44. (1995). Identification of the human beta A2 crystallin gene (CRYBA2): localization of the gene on human chromosome 2 and of the homologous gene on mouse chromosome 1. Genomics doi
  45. (1991). Inherited eye diseases: diagnosis and clinical management. doi
  46. Lens crystallins and their microbial homologs: structure, stability, and function. Crit Rev Biochem Mol Biol doi
  47. Lens crystallins: the evolution and expression of proteins for a highly specialized tissue. Annu Rev Biochem doi
  48. Linkage of polymorphic congenital cataract to the gamma-crystallin gene locus on human chromosome 2q33-35. Hum
  49. MA .A new betaA1-crystallin splice junction mutation in autosomal dominant cataract.
  50. 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. doi
  51. Missense mutations in MIP underlie autosomal dominant ’polymorphic’ and lamellar cataracts linked to 12q. doi
  52. Molecular basis of a progressive juvenile-onset hereditary cataract. Proc Natl Acad Sci doi
  53. (1995). Molecular biology and evolution of crystallins: gene recruitment and multifunctional proteins in the eye lens. Austin (TX): R G Landes,
  54. Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract. doi
  55. Mutation in the connexin 50 gene (GJA8) in a Russian family with zonular pulverulent cataract. doi
  56. Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts.
  57. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol
  58. Progressive juvenile-onset punctate cataracts caused by mutation of the gammaD-crystallin gene. doi
  59. Relationship between proteins encoded by three human gamma-crystallin genes and distinct polypeptides in the eye lens.
  60. (1996). Structure of the bovine eye lens gD( g IIIb)-crystallin at 1.95 Å Acta Cryst doi
  61. (1996). Structure of the bovine eye lens γD (γIIIb)-crystallin at 1.95 Å Acta Cryst doi
  62. (1999). Structure of the crystallins. Eye doi
  63. The crystallins: genes, proteins and diseases.
  64. (1999). The gamma-crystallins and human cataracts: a puzzle made clearer. doi
  65. (1998). The genetics of cataract: our vision becomes clearer. doi
  66. The genetics of childhood cataract.
  67. (1997). The x-ray structure of a mutant eye lens beta B2-crystallin with truncated sequence extensions. Protein Sci doi
  68. Weitere Ergebnisse der Spaltlampenmikroskopie des vorderen Bulbusabschnittes. III (Abschnitt-Fortsetzung). Angeborene und fruh aufgetretene Linsenveranderungen. Graefe Arch Klin Exp Ophthal doi

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