Genetic heterogeneity of primary open angle glaucoma and ocular hypertension: linkage to GLC1A associated with an increased risk of severe glaucomatous optic neuropathy.

Abstract

The GLC1A locus for autosomal dominant juvenile and middle age onset primary open angle glaucoma (OAG) has been mapped to chromosome lq21-q31. OAG, however, is a heterogeneous disease. We tested linkage of OAG and ocular hypertension (OHT), a major risk factor for OAG, to GLC1A in eight French families with multiple cases of juvenile and middle age onset OAG. There was strong evidence of genetic heterogeneity, four families being linked to GLC1A and two or three others being unlinked, depending on whether the complete OAG phenotype was analysed alone or jointly with OHT In initial linkage studies, disease onset consistently occurred before the age of 20.9 12-15 Subsequently, two large families were characterised, in which both juvenile OAG and middle age onset OAG were observed.'6 17 These findings indicated that the range of phenotypes determined by the GLClA chromosomal region could be broader than initially thought. However, GLC1A was also probably excluded in one family with middle age onset OAG,'8 and a second localisation (GLCIB) on proximal chromosome 2q was recently proposed.'9 Therefore, these results raised questions as to the role of the GLC1A locus in middle to late age onset OAG and OHT, which

Association of a single nucleotide polymorphism in the TIGR/MYOCILIN gene promoter with the severity of primary open‐angle glaucoma

“…Our present findings extend our previous observations showing that, in POAG families linked to GLC1A/TIGR/MYOC, clinical features were more severe and relatives of probands had an increased risk of developing glaucoma as opposed to isolated ocular hypertension (14). In these GLC1A-linked families, a mutation of the MYOC protein could be identified (8).…”

“…Because visual fields were not assessed in a standardized manner, a semi‐quantitative grading procedure was used. Scores on a five‐point scale were defined as previously [14]: 1, no alteration; 2, early defect; 3, arcuate defect; 4, advanced scotoma; 5, light perception only or no vision. These scores were assigned prior to genotyping and were compared with the nonparametric Mann–Whitney U‐test.…”

Variants in Optineurin Gene and Their Association with Tumor Necrosis Factor-α Polymorphisms in Japanese Patients with Glaucoma

“…The severity of the visual field defects was scored from 1 to 5 according to previously reported criteria. 28,29 The data obtained by two types of perimetry were combined using a five-point scale: 1, no alterations; 2, early defects; 3, moderate defects; 4, severe defects; and 5, light perception only or no light perception. The first four groups on this severity scale followed Kozaki's classification based on Goldmann perimetry, 30,31 or the classification was based on results of visual field perimetry (Humphrey Field Analyzer; Carl Zeiss Meditec, Dublin, CA).…”

The integrin α10 subunit: expression pattern, partial gene structure, and chromosomal localization

“…Several disease-related genes have been mapped to chromosome band 1q21, including the GLC1A locus for open-angle glaucoma (Brezin et al, 1997), the familial partial lipodystrophy locus (Peters et al, 1998), a target binding site for the Wilms' tumor suppressor 1 (WT1) gene (Negus et al, 1996), genes linked to hyperparathyroidism (Teh et al, 1996), nonsyndromic hearing impairment (Fagerheim et al, 1996), neural tube defects (Stanier et al, 1995), and multiple craniofacial anomalies (Leichtman et al, 1993). Nonrandom abnormalities of 1q21 → q25 are frequent in AIDS-related Burkitt's lymphoma-derived cell lines (Polito et al, 1995), and there is an overrepresentation of 1q21 → q23 in lipoma-like and soft-tissue sarcomas (Forus et al, 1995;Szymanska et al, 1997).…”