NOVEL MUTATIONS IN THE TIGR GENE IN EARLY AND LATE-ONSET OPEN-ANGLE GLAUCOMA

A gene for juvenile onset, open angle glaucoma (JOAG) has been localiz ed to chromosome 1q21-31 in several families. Mutations in the trabecu lar meshwork-induced glucocorticoid response protein (TIGR) gene, whic h maps to this region, recently have been found in families segregatin g both JOAG and a later onset form of primary open angle glaucoma (POA G), We have analysed the TIGR gene in two families; one Spanish family segregating autosomal dominant JOAG and an Irish family with a later onset form of autosomal dominant POAG, We have found a G-T transversio n in the first base of codon 426 in all affected members of the Spanis h family which results in a valine to phenylalanine amino acid substit ution. We have also found a G-A transition at the first base of codon 367 that segregates through all but one branch of the Irish family and results in a glycine to arginine amino acid substitution. Members of this family that carry the Gly367Arg change also share a common haplot ype that is neither present in any of the unaffected members of the fa mily, nor in the branch that does not segregate the mutation. Identifi cation of further mutations in the TIGR gene increases its importance in the etiology of open angle glaucoma. (C) 1998 Wiley Liss, Inc.