title: A stepwise strategy for rapid and cost-effective RB1 screening in Indian retinoblastoma patients.
abstract: India has the highest number of retinoblastoma (RB) patients among the developing countries owing to its increasing population. Of the patients with RB, about 40% have the heritable form of the disease, making genetic analysis of the RB1 gene an integral part of disease management. However, given the large size of the RB1 gene with its widely dispersed exons and no reported hotspots, genetic testing can be cumbersome. To overcome this problem, we have developed a rapid screening strategy by prioritizing the order of exons to be analyzed, based on the frequency of nonsense mutations, deletions and duplications reported in the RB1-Leiden Open Variation Database and published literature on Indian patients. Using this strategy for genetic analysis, mutations were identified in 76% of patients in half the actual time and one third of the cost. This reduction in time and cost will allow for better risk prediction for siblings and offspring, thereby facilitating genetic counseling for families, especially in developing countries.
authors.affiliation: Department of Molecular Genetics, Aravind Medical Research Foundation, Madurai, India.
authors.forename: Kannan
authors.initials: K
authors.lastname: Thirumalairaj
authors.affiliation: Department of Molecular Genetics, Aravind Medical Research Foundation, Madurai, India.
authors.forename: Aloysius
authors.initials: A
authors.lastname: Abraham
authors.affiliation: Department of Bioinformatics, Aravind Medical Research Foundation, Madurai, India.
authors.forename: Bharanidharan
authors.initials: B
authors.lastname: Devarajan
authors.affiliation: Department of Orbit, Oculoplasty and Oncology, Aravind Eye Hospital, Madurai, India.
authors.forename: Namrata
authors.initials: N
authors.lastname: Gaikwad
authors.affiliation: Department of Orbit, Oculoplasty and Oncology, Aravind Eye Hospital, Madurai, India.
authors.forename: Usha
authors.initials: U
authors.lastname: Kim
authors.affiliation: Advisor-Research, Aravind Medical Research Foundation, Madurai, India.
authors.forename: Veerappan
authors.initials: V
authors.lastname: Muthukkaruppan
authors.affiliation: Department of Molecular Genetics, Aravind Medical Research Foundation, Madurai, India.
authors.forename: Ayyasamy
authors.initials: A
authors.lastname: Vanniarajan
mesh_terms: D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D004252:DNA Mutational Analysis / Q000191:economics / Q000379:methods; D005260:Female; D016161:Genes, Retinoblastoma; D005820:Genetic Testing / Q000191:economics / Q000379:methods; D006801:Humans; D007194:India; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D060885:Multiplex Polymerase Chain Reaction / Q000191:economics; D019572:Retinal Neoplasms / Q000175:diagnosis* / Q000191:economics / Q000235:genetics; D012175:Retinoblastoma / Q000175:diagnosis* / Q000191:economics / Q000235:genetics; D013997:Time Factors