Retinal
Retinal
Inherited retinal degenerations (IRDs) are characterized by progressive dysfunction and death of rod and cone photoreceptor cells, leading to vision loss, and are one of the most genetically diverse groups of inherited disorders. Identifying the genetic cause of patients’ IRD has become especially important with the success of gene therapy trials. The specific genetic cause remains elusive in half of IRD patients, indicating many gene discoveries remain.
Muscle
Muscle
Inherited neuromuscular diseases represent diverse clinical phenotypes with the unifying feature of weakness; primary muscle disease alone has a combined population prevalence of over one in 3,000. Currently over 50% of neuromuscular disease patients cannot be provided with a genetic diagnosis even after extensive targeted screening of known genes, indicating that many causal genes remain undiscovered.
Neurodevelopmental
Neurodevelopmental
Neurodevelopmental disorders (NDDs) affect ~4-6% of the population and account for >5-10% of total healthcare costs, Mendelian NDDs remain a diagnostic dilemma because they are frequently difficult to distinguish from NDDs with more complex inheritance, like autism or epilepsy. Collectively NDDs comprise the biggest set of discoveries of Mendelian centers to date, but more than 50% of patients are still left undiagnosed, indicating that NDDs remain a fertile& area for novel gene discovery. To enrich for new genes we will focus primarily on cases with specific features (e.g. metabolic, degenerative, ataxia, microcephaly, syndromic) for which Mendelian causes far outweigh non-Mendelian ones.
Orphan
Orphan
A rare, or “orphan” disease is defined as a disease or disorder that affects less than 200,000 people in the United States at any given time.However, there are approximately 30 million people in the U.S. that are affected by a rare disease. We will recruit samples from patients with rare, undiagnosed diseases with a suspected Mendelian basis.
Cardiac
Cardiac
Inherited forms of cardiomyopathy, including hypertrophic (HCM) and dilated (DCM), are among the most common Mendelian diseases and are associated with risk for sudden cardiac death. HCM alone is the leading cause of sudden nontraumatic death in young adults. Although a number of genes have been identified for these disorders, the cause of over half of cases remain unknown even after comprehensive testing. In addition, congenital heart malformations are the most common birth defect and the most common cause of infant death, yet only 20% are diagnosable with known genetic causes.
Kidney
Kidney
Chronic kidney disease (CKD) is characterized by irreversible deterioration of renal function that gradually progresses to end-stage renal disease. The majority of CKD that presents before the age of 25 is caused by congenital anomalies of the kidneys and urinary tract (CAKUT), steroid-resistant nephrotic syndrome (SRNS), chronic glomerulonephritis and renal cystic ciliopathies. Variants in over 200 different monogenic genes have been associated with 70% of the most common causes of early-onset CKD.