一个先天性无虹膜家系PAX6基因突变研究

R240X mutation of the PAX6 gene in a Chinese family with congenital aniridia

目的对一个先天性无虹膜家系进行致病基因研究。方法采集患者外周静脉血，提取基因组DNA。采用微卫星标记物D11S904和D11S935对1个先天性无虹膜家系进行连锁分析；采用直接测序对PAX6基因全部14个外显子，以及外显子内含子拼接部进行序列分析。结果在微卫星位点D11S904获得LOD值为3．01。该家系患者PAX6基因第9外显子检出R240X突变，而家系正常人以及100名正常对照无此基因突变。结论R240X再发突变是导致先天性无虹膜的突变热点。

Objective To study the PAX6 gene mutation in a Chinese pedigree with congenital aniridia. Methods Linkage analysis was performed to the Chinese family with congenital aniridia using two microsatellite markers DllS904 and DllS935. Analysis of the PAX6 gene mutation was done by direct sequencing of the whole coding region and exon-intron boundaries of the PAX6 gene in all affected and unaffected individuals in the family. Results The significant Lod Score of 3.01 was acquired at DllS935. Direct DNA sequence analysis identified a 1080C to T change in exon 9 of the patients, resulting in an Arginine substitution by a stop codon at codon 240 of the PAX6 gene, which was absent in the unaffected individuals in the family and 100 normal controls. Conclusion Our results indicate that mutation p. Arg240Ter of the PAX6 is the genetic basis of the Chinese family with congenital aniridia.