Burdon Kathryn P, McKay James D, Wirth M Gabriela, Russell-Eggit Isabelle M, Bhatti Samira, Ruddle Jonathan B, Dimasi David, Mackey David A, Craig Jamie E
Department of Ophthalmology, Flinders University, Bedford Park, South Australia, Australia.
Mol Vis. 2006 Apr 18;12:367-71.
Congenital cataract is a significant cause of blindness worldwide. Many genes are known to cause the disorder. A large multigenerational pedigree was investigated for the genetic cause of a posterior polar autosomal dominant congenital cataract.
A genome wide scan was conducted in a large multigenerational family with autosomal dominant cataract to identify the linked region of the genome. The PITX3 gene was investigated through direct sequencing and detection of fluorescently labeled PCR products.
Linkage was detected to a region of chromosome 10q23-26 which contains the candidate gene PITX3. A segregating 17 bp insertion mutation was identified. This mutation was not identified in 100 additional unrelated sporadic and familial congenital cataract patients. No mutations of the PITX3 gene were identified in 9 families with posterior polar congenital cataract.
The 657ins17bp duplication of the PITX3 gene is the cause of the cataract phenotype in the large pedigree, however, this gene appears responsible for only a small proportion of congenital cataract in Australia.
先天性白内障是全球失明的一个重要原因。已知许多基因会导致该疾病。对一个大型多代家系进行了研究，以寻找后极性常染色体显性先天性白内障的遗传病因。
对一个患有常染色体显性白内障的大型多代家系进行全基因组扫描，以确定基因组的连锁区域。通过直接测序和检测荧光标记的PCR产物对PITX3基因进行研究。
检测到与10号染色体q23 - 26区域连锁，该区域包含候选基因PITX3。鉴定出一个17bp的插入突变。在另外100名无关的散发性和家族性先天性白内障患者中未发现此突变。在9个后极性先天性白内障家族中未鉴定出PITX3基因的突变。
PITX3基因的657ins17bp重复是这个大型家系中白内障表型的病因，然而，在澳大利亚，该基因似乎仅导致一小部分先天性白内障。
