Expert Reviewed By: Dr. Brandon Colby MD
Membranoproliferative glomerulonephritis type II (MPGN II), also known as dense deposit disease (DDD), is a rare kidney disorder characterized by uncontrolled activation of the alternative pathway of the complement system. This leads to the formation of dense deposits within the kidney's filtering units, called glomeruli, resulting in kidney damage and eventually kidney failure. Genetic factors play a significant role in the development of this disease, and understanding these factors can help in its diagnosis and management. This article will delve into the genetic aspects of MPGN II/DDD, focusing on the variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5), and explore the benefits of genetic testing for this disorder.
Genetic Factors in MPGN II/DDD: The Role of CFH and CFHR5
Research has shown that specific allele variants of the CFH and CFHR5 genes are associated with the development of MPGN II/DDD, implicating complement dysregulation in the disease's pathophysiology (1). The CFH gene is responsible for producing a protein called complement factor H, which plays a crucial role in regulating the alternative pathway of the complement system. Variations in this gene can lead to uncontrolled activation of the complement system, resulting in the formation of dense deposits and subsequent kidney damage (2).
Similarly, the CFHR5 gene is involved in the production of a protein called factor H-related protein 5, which is thought to play a role in modulating the activity of complement factor H. Variations in this gene can also contribute to the development of MPGN II/DDD (1). In one case study, a patient with MPGN II was found to have a prototypical complement genetic profile, supporting the hypothesis that dense deposit diseases involve dysregulation of the alternative pathway of complement activation (3).
Genetic Testing for MPGN II/DDD: A Valuable Diagnostic Tool
Confirming Diagnosis
Genetic testing can be a valuable tool in diagnosing MPGN II/DDD, as it can help confirm the presence of variations in the CFH and CFHR5 genes that are associated with the disease. This can be particularly useful in cases where the clinical presentation is unclear or when other diagnostic tests are inconclusive. By identifying the specific genetic factors involved, doctors can make a more accurate diagnosis and develop a targeted treatment plan for the patient.
Identifying At-Risk Family Members
As MPGN II/DDD has a genetic component, it is important to identify family members who may be at risk of developing the disease. Genetic testing can help determine if a person carries the specific allele variants associated with MPGN II/DDD, allowing for early intervention and monitoring. In some cases, such as in porcine MPGN type II, the disease is inherited as a simple autosomal recessive trait, meaning that both parents must carry the gene mutation for the offspring to be affected (4). Identifying at-risk individuals can help families make informed decisions about family planning and healthcare management.
Informing Treatment Options
Understanding the genetic factors involved in MPGN II/DDD can also help inform treatment options. As the disease is associated with uncontrolled activation of the alternative pathway of the complement cascade, therapies targeting this pathway may be effective in treating the condition (2). By identifying the specific genetic variations involved, doctors can develop a personalized treatment plan that targets the underlying cause of the disease, potentially leading to better outcomes for the patient.
Conclusion
Genetic testing for MPGN II/DDD can provide valuable insights into the underlying cause of the disease, aiding in diagnosis, identifying at-risk family members, and informing treatment options. By understanding the role of CFH and CFHR5 gene variations in the development of this rare kidney disorder, doctors and patients can work together to develop a targeted approach to managing the condition and improving the quality of life for those affected.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)