Purchase this article with an account.
M. Sarfarazi, T. Rezaie, A. Child, J. Thomas, R. Hitchings, E. Héon, T. Krupin, R. Ritch, J. Liebmann , E.Ilitchev, R. Crick; Optineurin Mutations in Patients With Low Pressure Glaucoma (LPG): No Evidence for E50K Founder Effect . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2148.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: We have previously reported mutations in Optineurin (OPTN) in a group of families with adult-onset LPG/POAG (Science 295:1077-9; 2002). We further aimed to screen additional LPG patients for mutations in this gene and to rule out the possibility of E50K as being a founder effect mutation. Methods: Genomic DNA from 440 LPG patients used to screen for OPTN mutations. So far, we fully sequenced 5 out of 13 coding exons in these patients. Additionally, in order to test for founder effect possibility of the E50K mutation, genomic DNA from normal and affected individuals of 7 families with this mutation were used to genotype 18 DNA markers from within a 2.65 Mb region flanking the OPTN gene. Results: Our mutation screening so far identified 2 new DNA alterations in OPTN exons 4 and 5. The first sequence alteration is a c.356C>G (P16A) in exon 4 of one LPG subject and the second is a c.585A>T (E92V) in exon 5 of another LPG patient. Both of theses DNA alterations were absent in 190 normal chromosomes. We also identified additional M98K and new polymorphisms in this gene. M98K was present in 33 out of 269 LPG patients (12.3%) as well as 2.1% of normal controls. Additionally, 3 LPG subjects were homozygote for Lysine at this position. Extensive genotyping of 7 families with E50K mutation did not identify any common haplotype thus confirming that E50K is a recurrent mutation in these families. Conclusions: We have previously reported mutations in OPTN as a disease-causing gene in 16.7% of familial adult-onset LPG/POAG, with E50K being the most frequent mutation (13.5%). The E50K is a recurrent mutation that has spontaneously risen several times. The new OPTN mutations reported here (P16A and E92V) are located within the coil and helix domains of optineurin protein. Supported by EY-09947 and M01RR-06192.
This PDF is available to Subscribers Only