The Mustafi lab is investigating the genetic basis of inherited retinal degenerations (IRDs) and potential for therapeutic intervention to prevent the progression of blindness. In the pediatric population, IRDs are a major cause of visual impairment and can be one of the first presenting features of a syndromic condition. Early genetic diagnosis of such conditions may mitigate morbidity and allow appropriate genetic counseling. Identification of disease-causing variants is essential and can lead to more timely and accurate diagnosis in children to properly assess their inclusion in emerging therapies. However, in approximately 20% of patients with well-defined clinical features of an autosomal recessive IRD, only one mutation is identified with initial exome sequencing. In such cases, genome sequencing of the disease gene at increased depth can reveal the second pathogenic variant in non-coding regions of the gene
The Mustafi laboratory is applying established short-read and emerging long-read sequencing technology to better understand pathogenic variants that lead to IRDs. Using blood samples from affected IRD patients and their families, his lab is able to carry out genome sequencing to identify novel pathogenic variants of disease and reconstruct disease haplotypes, which has implications for the interpretation of disease risks. The isolated blood samples can also be used to generate patient-specific stem cells to better study the pathogenicity of disease variants. Overall, the goal of the lab is to uncover the mechanistic details of IRDs to allow the development of targeted therapeutics to benefit patients treated by Dr. Mustafi.