The PITX3 gene in posterior polar congenital cataract in Australia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Burdon
Kathryn P
KP
Department of Ophthalmology, Flinders University, Bedford Park, South Australia, Australia. kathryn.burdon@flinders.edu.au
McKay
James D
JD
Wirth
M Gabriela
MG
Russell-Eggit
Isabelle M
IM
Bhatti
Samira
S
Ruddle
Jonathan B
JB
Dimasi
David
D
Mackey
David A
DA
Craig
Jamie E
JE
D001315:Australia; D002386:Cataract / Q000151:congenital* / Q000235:genetics*; D020090:Chromosome Segregation; D002879:Chromosomes, Human, Pair 10; D004251:DNA Transposable Elements; D005260:Female; D008040:Genetic Linkage; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*
D004251:DNA Transposable Elements; D018398:Homeodomain Proteins; D014157:Transcription Factors; C433629:homeobox protein PITX3