Nature Genetics
31, 276 - 278 (2002)
Published online: 24 June 2002; | doi:10.1038/ng921
Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataractLei Bu1, 2, 9, Yiping Jin3, 9, Yuefeng Shi1, Renyuan Chu3, Airong Ban4, Hans Eiberg5, Lisa Andres6, Haisong Jiang1, Guangyong Zheng1, Meiqian Qian1, Bin Cui1, Yu Xia1, Jing Liu2, Landian Hu1, Guoping Zhao1, Michael R. Hayden6, 7
& Xiangyin Kong1, 81
Shanghai Research Center of Biotechnology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200233, People's Republic of China. 2
University of Science and Technology of China, Hefei, People's Republic of China. 3
Department of Ophthalmology, EENT Hospital, Medical College of Fudan University, People's Republic of China. 4
Department of Ophthalmology, People's Hospital of Yichuan, Luoyang, People's Republic of China. 5
University of Copenhagen/Panum Institute, Copenhagen, Denmark. 6
Xenon Genetics, Burnaby, British Columbia, Canada. 7
University of British Columbia/Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada. 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. 9
These authors contributed equally to this work.
Correspondence should be addressed to Xiangyin Kong xykong@srcb.ac.cnCongenital 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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