OBJECTIVE: To investigate the phenotype and age-related penetrance of @entity725 ( @entity725 ) in Australian families with the @entity29714 mutation @entity69518 . METHOD AND DESIGN: Cross-sectional genetic study. Four unrelated pedigrees carrying the @entity69518 mutation were ascertained from more than 2000 consecutive cases of @entity725 in the @entity726 Inheritance Study in Tasmania and from families with @entity726 referred to the study from throughout Australia. Index cases and available family members were examined for signs of @entity726 , and the presence of the @entity29714 @entity69518 mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. RESULTS: From the 4 pedigrees carrying the @entity69518 mutation, 23 individuals with either @entity2790 ( @entity2790 ) or @entity725 were found, with a mean +/- SD age at diagnosis of 41.2 +/- 11.5 years, and a mean peak intraocular pressure of 31.7 +/- 9.9 mm Hg. A further 9 mutation carriers older than 18 years were studied who as yet showed no signs of @entity2790 or @entity725 (6 of these 9 were younger than 30 years). A single individual with @entity725 was identified who did not carry the @entity69518 mutation. For @entity69518 carriers, age-related penetrance for @entity2790 or @entity725 was 88% at age 30 years. A positive family history of @entity725 was present for 3 of the 4 index cases. Thirteen (57%) of the 23 @entity69518 carriers with @entity2790 or @entity725 had undergone @entity726 drainage surgery. Although the @entity726 in these families appears to be pressure dependent, 2 individuals showed optic disc cupping before detected elevation in intraocular pressure. One family was of British origin, with a different background haplotype from the other 3 families from Greece or Macedonia, who shared a common haplotype. CONCLUSIONS: The @entity29714 @entity69518 mutation is associated with @entity725 that, in the pedigrees studied, had a younger age at onset and higher peak intraocular pressure than in pedigrees with the more common @entity30607 mutation. In addition, @entity1 with @entity726 with the @entity69518 mutation were more likely to have undergone @entity726 drainage surgery.

@entity726 phenotype in pedigrees with the @entity29714 XXXX mutation.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity725 :: ('MESH:C562750', 'Disease') :: ['primary open-angle glaucoma', 'POAG'] @entity30607 :: ('p|SUB|Q|368|X', 'ProteinMutation') :: ['Gln368STOP'] @entity726 :: ('MESH:D005901', 'Disease') :: ['Glaucoma', 'glaucoma'] @entity2790 :: ('MESH:D009798', 'Disease') :: ['OHT', 'ocular hypertension'] @entity29714 :: ('4653', 'Gene') :: ['GLC1A', 'myocilin'] @entity69518 :: ('p|SUB|T|377|M', 'ProteinMutation') :: ['Thr377Met']
@entity69518 :: (p|SUB|T|377|M,ProteinMutation) :: ['Thr377Met']
