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Human Genetics

, Volume 117, Issue 5, pp 452–459 | Cite as

Locus heterogeneity in autosomal recessive congenital cataracts: linkage to 9q and germline HSF4 mutations

  • Tim Forshew
  • Colin A. Johnson
  • Shagufta Khaliq
  • Shanaz Pasha
  • Catherine Willis
  • Rashida Abbasi
  • Louise Tee
  • Ursula Smith
  • Richard C. Trembath
  • Syed Qasim Mehdi
  • Anthony T. Moore
  • Eamonn R. Maher
Original Investigation

Abstract

Isolated (non-syndromic) congenital cataract may be inherited as an autosomal dominant, autosomal recessive, or X-linked recessive trait. Considerable progress has been made in identifying genes and loci for dominantly inherited cataract, but the molecular basis for autosomal recessive disease is less well defined. Hence we undertook genetic linkage studies in four consanguineous Pakistani families with non-syndromic autosomal recessive congenital cataracts. In two families linkage to a 38 cM region 9q13-q22 was detected. Although a locus for recessive congenital cataracts had not been mapped previously to this region, the target interval encompasses the candidate region autosomal recessive adult-onset pulverulent cataracts (CAAR). The CAAR was mapped previously to 9q13-q22, and may therefore be allelic to non-syndromic autosomal recessive congenital cataracts. The other two families did not demonstrate linkage to 9q, but both had a region of homozygosity at 16q22 containing the heat shock transcription factor 4 (HSF4) gene. The HSF4 mutations have been reported in four families with autosomal dominant cataracts and, recently, in a single kindred with autosomal recessive congenital cataract. Mutation analysis of HSF4 revealed homozygous mutations (p.Arg175Pro and c.595_599delGGGCC, respectively) in the two families. These findings confirm that mutations in HSF4 may result in both autosomal dominant and autosomal recessive congenital cataract, and highlight the locus heterogeneity in autosomal recessive congenital cataract.

Keywords

Cataract Consanguinity Mutation Pakistan Sequence analysis HSF4 

Notes

Acknowledgements

We thank Birmingham United Hospitals Trust Fund and the Wellcome Trust for financial support.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Tim Forshew
    • 1
  • Colin A. Johnson
    • 1
  • Shagufta Khaliq
    • 2
  • Shanaz Pasha
    • 1
  • Catherine Willis
    • 3
  • Rashida Abbasi
    • 2
  • Louise Tee
    • 1
  • Ursula Smith
    • 1
  • Richard C. Trembath
    • 4
  • Syed Qasim Mehdi
    • 2
  • Anthony T. Moore
    • 3
  • Eamonn R. Maher
    • 1
  1. 1.Section of Medical and Molecular Genetics, Institute of Biomedical ResearchUniversity of BirminghamEdgbaston, BirminghamUK
  2. 2.Biomedical and Genetic Engineering DivisionDr. AQ Khan Research LaboratoriesIslamabadPakistan
  3. 3.Institute of OphthalmologyUniversity College LondonLondonUK
  4. 4.Division of Medical Genetics, Departments of Medicine and GeneticsUniversity of LeicesterLeicesterUK

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