Sequence alterations in RX in patients with microphthalmia, anophthalmia, and coloboma

[摘要] Purpose: Microphthalmia, anophthalmia,and coloboma are ocular malformations with a significant geneticcomponent. Rx is a homeobox gene expressed early in thedeveloping retina and is important in retinal cell fate specificationas well as stem cell proliferation. We screened a group of 24 patientswith microphthalmia, coloboma, and/or anophthalmia for RXmutations. Methods: We used standard PCR andautomated sequencing techniques to amplify and sequence each of thethree RX exons. Patients’ charts were reviewed for clinicalinformation. The pathologic impact of the identified sequence variantwas analyzed by computational methods using PolyPhen and PMut algorithms. Results: In addition to thepolymorphisms we identified a single patient with coloboma having aheterozygous nucleotide change (g.197G>C) in the first exon thatresults in a missense mutation of arginine to threonine at amino acidposition 66 (R66T). In silico analysis predicted R66T to be adeleterious mutation. Conclusions: Sequence variations in RXare uncommon in patients with congenital ocular malformations, but mayplay a role in disease pathogenesis. We observed a missense mutation inRX in a patient with a small, typical chorioretinal coloboma,and postulate that the mutation is responsible for the patient’sphenotype.

[学科分类] 生物化学/生物物理