University of Washington Karalis Johnson Retina Center

Seattle Children's Hospital

The Mustafi Lab is investigating the genetic basis of inherited retinal degenerations (IRDs) and potentials for therapeutic intervention to prevent 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.

The goal of the lab is to uncover the mechanistic details of IRDs to develop targeted therapies to benefit patient's visual needs.

Identification of disease-causing variants is essential and can lead to more timely and accurate diagnosis in patients 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 disease gene of interest.

The Mustafi Lab is applying established short-read and emerging long-read sequencing technology to better understand pathogenic variants that cause IRDs. Using blood samples from affected IRD patients and their families, the lab carries out genome sequencing to identify novel pathogenic variants of disease and reconstruct disease haplotypes, which has implications for the interpretation of disease risks. Isolated blood samples can also be used to generate patient-specific stem cells to better study the pathogenicity of disease variants.