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Nature Genetics
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Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract

Nature Geneticsvolume 31, pages276–278 (2002)Cite this article

Abstract

Congenital cataracts cause 10–30% of all blindness in children, with one-third of cases estimated to have a genetic cause1. Lamellar cataract is the most common type of infantile cataract2. We carried out whole-genome linkage analysis of Chinese individuals with lamellar cataract, and found that the disorder is associated with inheritance of a 5.11-cM locus on chromosome 16. This locus coincides with one previously described for Marner cataract3. We screened individuals of three Chinese families for mutations inHSF4 (a gene at this locus that encodes heat-shock transcription factor 4) and discovered that in each family, a distinct missense mutation, predicted to affect the DNA-binding domain of the protein, segregates with the disorder. We also discovered an association between a missense mutation and Marner cataract in an extensive Danish family. We suggest thatHSF4 is critical to lens development.

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Figure 1: Lens opacity and pedigree structure of the Chinese family I.
Figure 2: Expression and mutation analysis ofHSF4.
Figure 3: Mutation positions and evolutionary conservation ofHSF4.

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References

  1. Lund, A.M., Eiberg, H., Rosenberg, T. & Warburg, M. Autosomal dominant congenital cataract; linkage relations; clinical and genetic heterogeneity.Clin. Genet.41, 65–69 (1992).

    Article CAS PubMed  Google Scholar 

  2. Falls, H.F. Developmental cataracts: results of surgical treatment of 131 cases.Arch. Ophthalmol.29, 210–213 (1943).

    Article  Google Scholar 

  3. Eiberg, H. et al. Marner's cataract (CAM) assigned to chromosome 16: linkage to haptoglobin.Clin. Genet.34, 272–275 (1988).

    Article CAS PubMed  Google Scholar 

  4. Marner, E. A family with eight generations of hereditary cataract.Acta Ophthalmol. (Copenh)27, 537–551 (1949).

    Article  Google Scholar 

  5. Nakai, A. et al.HSF4, a new member of the human heat shock factor family which lacks properties of a transcriptional activator.Mol. Cell Biol.17, 469–481 (1997).

    Article CAS PubMed PubMed Central  Google Scholar 

  6. Tanabe, M. et al. The mammalianHSF4 gene generates both an activator and a repressor of heat shock genes by alternative splicing.J. Biol. Chem.274, 27845–27856 (1999).

    Article CAS PubMed  Google Scholar 

  7. Bagchi, M., Ireland, M., Katar, M. & Maisel, H. Heat shock proteins of chicken lens.J. Cell Biochem.82, 409–414 (2001).

    Article CAS PubMed  Google Scholar 

  8. Bagchi, M., Katar, M. & Maisel, H. Heat shock proteins of adult and embryonic human ocular lenses.J. Cell Biochem.84, 278–284 (2002).

    Article CAS PubMed  Google Scholar 

  9. Torres, F.A., Bonner, J.J. Genetic identification of the site of DNA contact in the yeast heat shock transcription factor.Mol. Cell Biol.15, 5063–5070 (1995).

    Article CAS PubMed PubMed Central  Google Scholar 

  10. Monaghan, K.G., Van Dyke, D.L., Wiktor, A. & Feldman, G.L. Cytogenetic and clinical findings in a patient with a deletion of 16q23.1: first report of bilateral cataracts and a 16q deletion.Am. J. Med. Genet.73, 180–183 (1997).

    Article CAS PubMed  Google Scholar 

  11. Hartl, F.U. Molecular chaperones in cellular protein folding.Nature381, 571–579 (1996).

    Article CAS PubMed  Google Scholar 

  12. Bukau, B. & Horwich, A.L. The Hsp70 and Hsp60 chaperone machines.Cell92, 351–366 (1998).

    Article CAS PubMed  Google Scholar 

  13. Berry, V. et al. α-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans.Am. J. Hum. Genet.69, 1141–1145 (2001).

    Article CAS PubMed PubMed Central  Google Scholar 

  14. Straatsma, B.R., Foos, R.Y., Horwitz, J., Gardner, K.M. & Pettit, T.H. Aging-related cataract: laboratory investigation and clinical management.Ann. Intern. Med.102, 82–92 (1985).

    Article CAS PubMed  Google Scholar 

  15. Fawcett, T.W., Sylvester, S.L., Sarge, K.D., Morimoto, R.I. & Holbrook, N.J. Effects of neurohormonal stress and aging on the activation of mammalian heat shock factor 1.J. Biol. Chem.269, 32272–32278 (1994).

    CAS PubMed  Google Scholar 

  16. Xiao, S. et al. Refinement of the locus for autosomal dominant hereditary gingival fibromatosis (GINGF) to a 3.8-cM region on 2p21.Genomics68, 247–252 (2000).

    Article CAS PubMed  Google Scholar 

  17. Lathrop, G.M., Lalouel, J.M., Julier, C. & Ott, J. Strategies for multilocus linkage analysis in humans.Proc. Natl Acad. Sci. USA81, 3443–3446 (1984).

    Article CAS PubMed PubMed Central  Google Scholar 

  18. Cottingham, R.W. Jr, Idury, R.M. & Schaffer, A.A. Faster sequential genetic linkage computations.Am. J. Hum. Genet.53, 252–263 (1993).

    PubMed PubMed Central  Google Scholar 

  19. Schaffer, A.A., Gupta, S.K., Shriram, K. & Cottingham, R.W. Jr, Avoiding recomputation in linkage analysis.Hum. Hered.44, 225–237 (1994).

    Article CAS PubMed  Google Scholar 

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Acknowledgements

We are grateful to all of the individuals described here for their contribution to this study. We thank F. Francis and Z. Chen for critical reading of this manuscript, and C. Lopez-Otin and F. Hejtmancik for providing samples for mutation analysis. This work was supported by the National High Technology “863” Programs of China, the National Science Fund for Distinguished Young Scholars and Xenon Genetics.

Author information

Author notes

  1. Lei Bu and Yiping Jin: These authors contributed equally to this work.

Authors and Affiliations

  1. Shanghai Research Center of Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200233, People's Republic of China

    Lei Bu, Yuefeng Shi, Haisong Jiang, Guangyong Zheng, Meiqian Qian, Bin Cui, Yu Xia, Landian Hu, Guoping Zhao & Xiangyin Kong

  2. University of Science and Technology of China, Hefei, People's Republic of China

    Lei Bu & Jing Liu

  3. Department of Ophthalmology, EENT Hospital, Medical College of Fudan University, People's Republic of China

    Yiping Jin & Renyuan Chu

  4. Department of Ophthalmology, People's Hospital of Yichuan, Luoyang, People's Republic of China

    Airong Ban

  5. University of Copenhagen/Panum Institute, Copenhagen, Denmark

    Hans Eiberg

  6. Xenon Genetics, Burnaby, British Columbia, Canada

    Lisa Andres & Michael R. Hayden

  7. University of British Columbia/Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada

    Michael R. Hayden

  8. Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Second Medical University, Shanghai, 200025, People's Republic of China

    Xiangyin Kong

Authors
  1. Lei Bu
  2. Yiping Jin
  3. Yuefeng Shi
  4. Renyuan Chu
  5. Airong Ban
  6. Hans Eiberg
  7. Lisa Andres
  8. Haisong Jiang
  9. Guangyong Zheng
  10. Meiqian Qian
  11. Bin Cui
  12. Yu Xia
  13. Jing Liu
  14. Landian Hu
  15. Guoping Zhao
  16. Michael R. Hayden
  17. Xiangyin Kong

Corresponding author

Correspondence toXiangyin Kong.

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Competing interests

The authors declare no competing financial interests.

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Bu, L., Jin, Y., Shi, Y.et al. Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract.Nat Genet31, 276–278 (2002). https://doi.org/10.1038/ng921

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