Yamada K, Tomita H, Yoshiura K, Kondo S, Wakui K, Fukushima Y, Ikegawa S, Nakamura Y, Amemiya T, Niikawa N
Department of Human Genetics, Nagasaki University School of Medicine, Japan.
Eur J Hum Genet. 2000 Jul;8(7):535-9. doi: 10.1038/sj.ejhg.5200485.
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 (Zmax) of 3.61 with a recombination fraction (theta) 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.
我们通过使用微卫星标记进行全基因组两点连锁分析，将先前报道的一种新型常染色体显性后极性白内障（CPP3）的基因座定位于20p12 - q12。CPP3的特征为进行性、盘状、后囊下混浊。在一个日本家族的10名成员中发现了这种疾病，并以常染色体显性方式在四代人中传递。对于标记D20S917、D20S885和D20S874，我们获得了最大对数优势分数（Zmax）为3.61，重组分数（θ）为0.00。单倍型分析将疾病基因定位在20号染色体p12 - q12上D20S851和D20S96基因座之间15.7厘摩的区间内。由于编码晶状体特异性串珠状细丝结构蛋白1（丝状肌动蛋白）的BFSP1已定位在CPP3区域附近，我们对其整个编码区进行了序列分析。然而，在CPP3患者中未检测到碱基替换或缺失。CPP3基因座定位于20p12 - q12不仅扩展了我们对常染色体显性后极性白内障遗传异质性的理解，也是疾病基因定位克隆的一条线索。
