Human pituitary homeobox-3 gene in congenital cataract in a Chinese family.

Objectives: Congenital cataract is the common cause of world blindness. It is generally inherited as an autosomal recessive trait and has various phenotypes. This study aimed to explore the gene responsible for autosomal recessive congenital cataract in a Chinese family, and to investigate the functional and cellular consequences of the mutation.

Methods: A four-generation Chinese family with autosomal recessive congenital cataract was included in the study. A genome wide scan and linkage analysis were performed in the chromosomal region of Pituitary homeobox 3 (PITX3) to identify the linked region of the genome. And sequence analysis of PITX3 gene was also investigated using BigDye Terminator mix 3.0 and SeqScape Software 2.5.

Results: The genome wide scan and linkage analysis identified a disease-haplotype interva. The maximum logarithm of odds LOD score was (Zmax) 3.11 at marker D10S1693 (θmax=0.00), flanked by D10S1680 and D10S467, which included the PITX3 gene. Sequencing revealed a splice site mutation, G→A, at D10S1680 and D10S467, which co-segregated with all the affected members of this family.

Conclusions: The 543delG is a novel mutation in PITX3 causing an autosomal recessive congenital cataract.