An autosomal dominant posterior polar cataract locus maps to human chromosome 20p12–q12

Abstract

We assigned the locus for a previously reported new type of autosomal dominant posterior polar cataract (CPP3) to 20p12-q12 by a genome-wide two-point linkage analysis with microsatellite markers. CPP3 is characterized by progressive, disc-shaped, posterior subcapsular opacity. The disease was seen in 10 members of a Japanese family and transmitted in an autosomal dominant fashion through four generations. We obtained a maximum lod score (Z max ) of 3.61 with a recombination fraction (θ) of 0.00 for markers D20S917, D20S885 and D20S874. Haplotype analysis gave the disease gene localization at a 15.7-cM interval between D20S851 and D20S96 loci on chromosome 20p12-q12. Since the BFSP1 that encodes the lens-specific beaded filament structural protein 1 (filensin) has been mapped around the CPP3 region, we performed sequence analysis on its entire coding region. However, no base substitution or deletion was detected in the CPP3 patients. The mapping of the CPP3 locus to 20p12-q12 not only expands our understanding of the genetic heterogeneity in autosomal dominant posterior polar cataracts but also is a clue for the positional cloning of the disease gene.

Cell death triggered by a novel mutation in the alphaA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q

“…To date at least 20 independent loci for clinically diverse forms of Mendelian cataract have been mapped on 14 human chromosomes. 4 No causative genes have been reported at the dominant loci on chromosomes 1p, 5,6 2p, 7 15q, 8 17p, 9 17q24 10 and 20p 11 or at the recessive loci on 3p 12 and 9q. 13 However, underlying mutations have been identified in seven crystallin genes including: the alpha-crystallin genes located on 11q (CRYAB) 14 and 21q (CRYAA), 15,16 three beta-crystallin genes located on 17q (CRYBA3/A1) 17,18 and 22q (CRYBB2, CRYBB1) 19 -22 and two gamma-crystallin genes (CRYGC, CRYGD) located on 2q.…”

A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance

“…8 Five additional loci have been described on chromosomes 1pter-p36.1, 9 15q21-q22, 10 17p13, 11 17q24, 12 and 20p12-q12. 13 We used a linkage approach to investigate these 13 genes and five loci in a large pedigree from Victoria, Australia, with zonular pulverulent cataract with the aim of identifying the causative mutation.…”

Recurrent 17 bp duplication in PITX3 is primarily associated with posterior polar cataract (CPP4)

“…13 Subsequently, further loci for posterior polar cataract were mapped: CPP1 on 1p36, 14 CPP2 on 11q21, 15 and CPP3 on chromosome 20p12. 16 We now define CPP4 on the long arm of chromosome 10, encompassing the PITX3 gene, a In the last few years a number of mutations in transcription factors have been shown to cause ASMD and cataracts: PAX6, FOXE3, EYA1, MAF, and PITX3. PAX6 mutations were identified in heterogeneous anterior-segment malformations in a family including Rieger and Peter anomalies.…”