A V235L Mutation of the Human BEST1 Gene Associated with Best Macular Dystrophy with Intra-familial Clinical Variations

Abstract

Introduction: Best vitelliform macular dystrophy (BVMD) accounts for 1% of all cases of macular degeneration resulting in progressive loss of central vision. In this work we sought to evaluate the clinical and genetic background in a two generation pedigree of autosomal dominant BVMD for clinical management and follow up. To our knowledge this is the first report on association of Bestrophin 1 (BEST1) mutation with BVMD in an Indian family. Case report: Complete ophthalmic examination done in a family with a complaint of impaired vision revealed the presence of yellow-orange yolk like lesions in the macula upon fundus examination. Further investigations through EOG revealed decreased Arden ratio. Besides the proband, two other members namely, mother and siblings were also affected in the family. Follow up clinical examination was done after three years to clinically document the progression of the disease, OCT examination was done in addition during follow up studies. Genomic DNA samples of the affected family members showed a sequence variation, c.703 G>T transversion in exon # 6 which results in substitution of valine by polar leucine as V235L. This variant was not observed in the unaffected father and 65 ethnically matched controls. Follow up clinical examination of the proband and his sib showed rapid progression of the disease. Conclusions: We report for the first time an attempt on genetic diagnosis in a case of Best disease from Indian ethnicity. The disease condition revealed a rapid progression in the proband as compared to his mother, depicting severity of the disease in successive generation. The study prompts the need for genetic prognosis to identify predisposed/ susceptible individuals to enable proper counseling to the family members about the disease.