Aramati B. M. Reddy

Myocilin gene implicated in primary congenital glaucoma

Primary congenital glaucoma (PCG) has been associated with CYP1B1 gene (2p21), with a predominantly autosomal recessive mode of inheritance. Our earlier studies attributed CYP1B1 mutations to only 40% of Indian PCG cases. In this study, we included 72 such PCG cases where CYP1B1 mutations were detected in only 12 patients in heterozygous condition, implying involvement of other gene(s). On screening these patients for mutations in myocilin (MYOC), another glaucoma‐associated gene, using denaturing high‐performance liquid chromatography followed by sequencing, we identified a patient who was double heterozygous at CYP1B1 (c.1103G>A; Arg368His) and MYOC (c.144G>T; Gln48His) loci, suggesting a digenic mode of inheritance of PCG. In addition, we identified the same MYOC mutation, implicated for primary open angle glaucoma, in three additional PCG patients who did not harbor any mutation in CYP1B1. These observations suggest a possible role of MYOC in PCG, which might be mediated via digenic interaction with CYP1B1 and/or an yet unidentified locus associated with the disease.

PAX6 gene mutations and genotype-phenotype correlations in sporadic cases of aniridia from India.

In order to understand the underlying molecular genetic defect causing aniridia in India, eight probands from sporadic cases were screened for all 14 exons of the PAX6 gene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Direct sequencing of the SSCP variants revealed a nonsense mutation (R317X) in the eleventh exon leading to a premature termination of the PAX6 protein in the proline-serine-threonine (PST)-rich domain in two probands. Another proband exhibited an intronic polymorphism (IVS 9–12 C-T). The mutation resulted in loss of function of the PAX6 protein along with variable phenotypic manifestations in the probands. This is the first report describing a PAX6 gene mutation in aniridia cases from India and highlights the variable expressivity in phenotypes due to haploinsufficiency.