OPTN gene: profile of patients with glaucoma from India.

PURPOSE: Optineurin gene (OPTN) mutations are reported in primary open angle glaucoma patients (POAG) from different populations. The coding and noncoding regions of OPTN were screened for mutations in 100 Indian high tension glaucoma patients (HTG). The frequency of the OPTN M98K mutation in an additional 120 patients (70 HTG and 50 normal tension glaucoma [NTG]) was analyzed by restriction enzyme digestion. METHODS: The HTG patients (about 40 years of age) were characterized by open angles on gonioscopy, with raised intraocular pressure (IOP) more than 21 mmHg (<21 mmHg on office diurnal phasing for NTG), and typical glaucomatous disc changes with corresponding visual field defects in the absence of any secondary cause. One hundred HTG patients and controls were screened for OPTN mutations by direct sequencing using an ABI prism 310/3100 Avant genetic analyzer. The M98K status was analyzed by restriction enzyme digestion with StuI. A genotype/phenotype correlation was also attempted for OPTN sequence alterations with clinical parameters such as age at diagnosis, intraocular pressure, cup:disc ratio, etc. The putative change in the transcription factor binding site for the IVS7 +24G>A polymorphism was attempted with AliBaba software (version 2.1). RESULTS: Six sequence alterations were observed in the 100 POAG patients by direct sequencing. The M98K substitution was observed in a total of 10 patients (7/170 HTG and 3/50 NTG) contributing to 4.1% in HTG and 6% in the NTG group and not in the controls. The IVS7+24G>A nucleotide change showed a significant difference in the HTG group (7/100) when compared to the control group (0/100) and found to be associated with increased IOP at diagnosis (p=0.03). The IVS7+24G>A polymorphism resulted in the creation of binding sites for transcription factors NF-1 and CPE that were not present in the wild type. CONCLUSIONS: The current study suggests a possible role of SNPs rather than mutations in OPTN in POAG pathology in the Indian population.

Low frequency of myocilin mutations in Indian primary open-angle glaucoma patients.

Glaucoma is one of the major causes of blindness in the Indian population. Mutations in the myocilin (MYOC) gene have been reported in different populations. However, reports on MYOC mutations in Indian primary open-angle glaucoma (POAG) patients and juvenile open-angle glaucoma (JOAG) patients are sparse. We therefore screened 100 unrelated POAG/JOAG patients for MYOC mutations. Patients with POAG/JOAG were clinically diagnosed. Genomic DNA from such patients was collected and studied for MYOC mutations by direct sequencing. Nucleotide variations were compared with unrelated healthy controls by restriction enzyme digestion. Secondary structure prediction for the sequence variants was performed by Chou-Fasman method. A novel mutation in exon 1 (144 G-->Alpha) resulting in Gln48His substitution was observed in 2% of the patients. Four other polymorphisms were also observed. The novel mutation was seen in four other affected family members of a JOAG patient. The novel mutation was found to alter the secondary structure in the glycosaminoglycan initiation site of the protein. MYOC mutations were found in 2% of the population studied. MYOC gene may not be playing a significant role in causing POAG in the Indian population.

Genetic profile of 81 retinoblastoma patients from a referral hospital in southern India.

PURPOSE: To determine chromosomal abnormalities and inheritance pattern in patients with retinoblastoma from a referral hospital in southern India. MATERIALS AND METHODS: Eighty-one retinoblastoma patients from 78 families were included in this study. Peripheral venous blood was taken for chromosomal analysis and pedigree was ascertained for segregation analysis. RESULTS: Male to female ratio was 1.7:1, 55.56% were bilateral retinoblastoma, the mean age of onset was 12.37 months in bilateral and 33.07 months in unilateral cases (p=0.048). Majority (90.12%) had sporadic inheritance and 6.17% had autosomal dominant inheritance. In chromosomal abnormalities, 8.33% had 13q14 deletion, three cases had de novo balanced translocations. CONCLUSION: The age of onset of the disease was much earlier in the bilateral cases compared to unilateral cases. Sporadic inheritance was predominant while only a small percentage of patients had autosomal dominant inheritance. The percentage of patients with 13q14 deletion was higher than reported in the literature and three novel chromosomal translocations were observed. This is one of the largest series of cases reported from India.