SCIENTIFIC REPORT

The telomere of human chromosome 1p contains at least two independent autosomal dominant congenital cataract genes

J D McKay^1,2, B Patterson¹, J E Craig^1,3,4, I M Russell-Eggitt⁵, M G Wirth⁶, K P Burdon^1,7, A W Hewitt¹, A C Cohn³, Y Kerdraon³ and D A Mackey^1,3

¹ Menzies Centre for Population Health Research, University of Tasmania, Hobart, Australia
² Genome analysis team, International Agency for Research on Cancer, Lyons, France
³ Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Australia
⁴ Department of Ophthalmology, Flinders University, Flinders Drive, Bedford Park, South Australia
⁵ Great Ormond St Hospital for Children, London, UK
⁶ Department of Ophthalmology, Royal Children’s Hospital, Melbourne, Australia
⁷ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA

Correspondence to:
Correspondence to:
Associate Professor David Mackey
The Royal Victorian Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, VIC 3002, Australia; d.mackey{at}utas.edu.au

Aims: Multiple genetic causes of congenital cataract have been identified, both as a component of syndromes and in families that present with isolated congenital cataract. Linkage analysis was used to map the genetic locus in a six generation Australian family presenting with total congenital cataract.

Methods: Microsatellite markers located across all known autosomal dominant congenital cataract loci were genotyped in all recruited family members of the Tasmanian family. Both two point and multipoint linkage analysis were used to assess each locus under an autosomal dominant model.

Results: Significant linkage was detected at the telomere of the p arm of chromosome 1, with a maximum two point LOD of 4.21 at marker D1S507, a maximum multipoint exact LOD of 5.44, and an estimated location score of 5.61 at marker D1S507. Haplotype analysis places the gene inside a critical region between D1S228 and D1S199, a distance of approximately 6 megabases. The candidate gene PAX7 residing within the critical interval was excluded by direct sequencing in affected individuals.

Conclusion: This is the third report of congenital cataract linkage to 1ptel. The critical region as defined by the shared haplotype in this family is clearly centromeric from the Volkmann cataract locus identified through study of a Danish family, indicating that two genes causing autosomal dominant congenital cataract map to the telomeric region of chromosome 1p.

Abbreviations: ADCC, autosomal dominant congenital cataract; PCR, polymerase chain reaction; SNP, single nucleotide polymorphism

Keywords: congenital cataract; genetics; chromosome; telomere; linkage

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• Shiels, A., Hejtmancik, J. F. (2007). Genetic Origins of Cataract. Arch Ophthalmol 125: 165-173 [Full Text]