title: Primary open angle glaucoma due to T377M MYOC: Population mapping of a Greek founder mutation in Northwestern Greece.
abstract: BACKGROUND
  Mutations in the MYOC gene have been shown to explain 5% of unrelated primary open angle glaucoma (POAG) in different populations. In particular, the T377M MYOC mutation has arisen at least three separate times in history, in Great Britain, India, and Greece. The purpose of this study is to investigate the distribution of the mutation among different population groups in the northwestern region of Greece.
  
  
  METHODS
  We explored the distribution of the "Greek" T377M founder mutation in the Epirus region in Northwestern Greece, which could be its origin. Genotyping was performed in POAG cases and controls by PCR amplification of the MYOC gene, followed by digestion with restriction enzyme. Statistical analyses were performed by an exact test, the Kaplan-Meier method and the t-test.
  
  
  RESULTS
  In the isolated Chrysovitsa village in the Pindus Mountains, a large POAG family demonstrated the T377M mutation in 20 of 66 family members while no controls from the Epirus region (n = 124) carried this mutation (P < 0.001). Among other POAG cases from Epirus, 2 out of 14 familial cases and 1 out of 80 sporadic cases showed the mutation (P = 0.057). The probability of POAG diagnosis with advancing age among mutation carriers was 23% at age 40, and reached 100% at age 75. POAG patients with the T377M mutation were diagnosed at a mean age of 51 years (SD +/- 13.9), which is younger than the sporadic or familial POAG cases: 63.1 (SD +/- 11) and 66.8 (SD +/- 9.8) years, respectively.
  
  
  CONCLUSIONS
  The T377M mutation was found in high proportion in members of the Chrysovitsa family (30.3%), in lower proportion in familial POAG cases (14.2%) and seems rare in sporadic POAG cases (1.2%), while no controls (0%) from the Epirus region carried the mutation. Historical and geographical data may explain the distribution of this mutation within Greece and worldwide.
authors.affiliation: Department of Ophthalmology, University of Ioannina, School of Medicine, Ioannina, Greece. gkitsos@cc.uoi.gr
authors.forename: George
authors.initials: G
authors.lastname: Kitsos
authors.forename: Zacharias
authors.initials: Z
authors.lastname: Petrou
authors.forename: Maria
authors.initials: M
authors.lastname: Grigoriadou
authors.forename: John R
authors.initials: JR
authors.lastname: Samples
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Haris
authors.initials: H
authors.lastname: Kokotas
authors.forename: Aglaia
authors.initials: A
authors.lastname: Giannoulia-Karantana
authors.forename: David A
authors.initials: DA
authors.lastname: Mackey
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wirtz
authors.forename: Marilita
authors.initials: M
authors.lastname: Moschou
authors.forename: John P A
authors.initials: JP
authors.lastname: Ioannidis
authors.forename: Michael B
authors.initials: MB
authors.lastname: Petersen
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