Myoc Gene Analysis in Patients Affected by Congenital Glaucoma Who Are Carriers of Only One Cyp1b1 Mutation

Abstract

Purpose: : Congenital glaucoma (CG) represents 0.01 to 0.04% of cases of severe blindness. Prevalence at birth is 1/10000. The mode of inheritance is autosomic recessive with variable penetrance, even if the disease has been described as poligenic and multifactorial. Linkage studies have shown a locus in the 2p21 region where the CYP1B1 gene was found mutated in a large part of CG patients. The mutation frequency in 40% of the pathological subjects hypothesizes the presence of one or more genes implicated in the pathology. In fact two other loci were identified on chromosomes 1 and 14, but the related genes are presently not known. Recent studies have reported CG cases with a mutation in CYP1B1 as well as in myocillin gene (MYOC/TIGR), associated with the juvanile form of glaucoma (JOAG); few JOAG patients were also carriers of mutations in the two genes proving a digenic inheritance. The aim of this study is to perform the MYOC/TIGR analysis in all the CG patients without or with only one mutation in CYP1B1 gene.

Methods: : DNA analysis was performed to identify the presence of CYP1B1 gene.

Results: : We found two new aminoacidic variants in patients hetherozygotes for the most common G61E mutation in CYP1B1. The two variants (A447V, R76K) are localized in a highly conserved protein region.

Conclusions: : This finding could suggest a presence of a digenic inheritance because of the presence of a double hetherozygote (CYP1B1/MYOC). Since frequence data of these two new aminoacidic variants are unknown, we are assessing their presence in a normal population. The segregation study of A447V identified that the variation derives from the healthy parent. We found no MYOC variants in all the others CYP1B1 hetherozygous patients.

Keywords: genetics • linkage analysis • mutations