遗传性先天无虹膜患者的PAX6基因新突变(c．1286del C)

A novel PAX6 mutation (c.1286delC) in the patients with hereditary congenital aniridia

为了研究遗传性先天无虹膜(Hereditary congenital aniridia)患者发病的分子遗传学机制,采用PCR扩增PAX6基因编码区的11个外显子(exon4-13)及外显子和内含子相连接的区域、PCR产物直接测序的方法对1个遗传性先天无虹膜家系的所有成员进行了遗传突变分析。结果表明,在家系中两个患者的PAX6基因exon11均存在c.1286delC新突变。此单个碱基的缺失造成了移码突变,导致肽链自309位氨基酸开始产生一段含55个氨基酸的异常肽段,并产生提前终止密码子(Premature termination codon,PTC),使PAX6蛋白羧基端的59个氨基酸缺失。另外,通过PCR-RFLP分析的方法对家系中所有正常成员和50名中国汉族健康对照个体基因组DNA进行分析均未检测到该突变。

To study the molecular genetic mechanism of hereditary congenital aniridia, the entire coding exons （exon 4-13） of PAX6 gene and the flanking exon-intron junctions were amplified through PCR from the genomic DNA of all the two patients in a Chinese family with aniridia. PCR products were purified from agarose gel and sequenced. In both patients, a novel deletion mutation （c. 1286delC） in exon 11 was identified. Compared with the normal product of PAX6 gene, this mutation caused frame shifting, and generated a novel 55 amino acid peptide from codon 309. This deletion also resulted in a premature termination codon （PTC） and preterminated peptide synthesis. Meanwhile, this mutation was absent in all the unaffected family members and 50 normal control individuals through PCR-RFLE