The power of homozygosity mapping: discovery of new genetic defects in patients with retinal dystrophy

Retinal dystrophies (RD) represent a group of inherited ophthalmic diseases, which are characterized by dysfunction or progressive loss of photoreceptor cells, often accompanied by fundus abnormalities. To date, approximately 115 genes are known to be mutated in these diseases that together are estimated to account for ∼50% of the inherited RD. Knowledge of the genetic defect used to be beneficial for the patient only in terms of genetic counseling, and receiving a more accurate disease diagnosis and prognosis. The first successful clinical trials using gene augmentation therapy in RD patients with RPE65 mutations however have given an enormous boost to the development of several types of genetic therapies for RD. As a consequence, the identification of the genetic causes of RD has become more important than ever, also for the individual patient. One of the methods to discover novel mutations is genome-wide homozygosity mapping. This method has been a regularly used method to identify the genetic defect in patients from consanguineous families. In this mini-review, we will provide an overview of our own research that leads to the conclusion that homozygosity mapping can also be a powerful method to identify the genetic defect in patients from nonconsanguineous families.