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J Med Genet 42:706-710 doi:10.1136/jmg.2004.028274
  • Short report

Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans

  1. H Sun1,*,
  2. Z Ma1,*,
  3. Y Li3,
  4. B Liu2,
  5. Z Li1,
  6. X Ding3,
  7. Y Gao3,
  8. W Ma1,
  9. X Tang1,
  10. X Li1,
  11. Y Shen4
  1. 1Eye Centre of Tianjin Medical University, Tianjin, China
  2. 2National Centre of Human Genome Research (Beijing), Beijing, China
  3. 3Zhoukou Eye Hospital, Henan, China
  4. 4National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China
  1. Correspondence to:
 Professor Yan Shen
 National Centre of Human Genome Research (Beijing), North Yongchang Road BDA, Beijing 100176, China; shenyms.imicams.ac.cn
  • Accepted 16 December 2004
  • Revised 15 December 2004

Abstract

Background: Congenital or childhood cataract is clinically and genetically a highly heterogeneous lens disorder in children. Autosomal dominant inheritance is most common.

Objective: To report the identification of a mutation in the human CRYGS gene.

Subjects and methods: A large six generation family affected by progressive polymorphic cortical cataract was investigated. After excluding loci for known cataract candidate genes using 39 fluorescent microsatellite markers, a whole genome scan was carried out.

Results: The disease was associated with inheritance of a 20.7 cM locus on chromosome 3q26.3-qter, with a maximum LOD score of 6.34 (θ = 0) at marker D3S1602. Haplotype analysis indicated that the disease gene lay at approximately 2.8 Mb physical intervals between D3S1571 and D3S3570 and contained CRYGS on 3q27.3. By sequencing the CRYGS gene, a distinct 1619G→T (AC068631) heterozygous missense mutation in exon 2 was identified, co-segregating with the disease phenotype in this family and resulting in a glycine (GGC) to valine residue (GTC) substitution in codon 18 (NP_060011).

Conclusions: This report is the first description of a mutation in CRYGS with autosomal dominant cataract in humans.

Footnotes

  • * Huimin Sun and Zhiwei Ma contributed equally to this work

  • Competing interests: none declared