Letter | Published:

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

Nature Genetics volume 31, pages 276278 (2002) | Download Citation

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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 in HSF4 (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 that HSF4 is critical to lens development.

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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

    • Lei Bu
    •  & Yiping Jin

    These authors contributed equally to this work.

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

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xiangyin Kong.

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DOI

https://doi.org/10.1038/ng921

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