The period between the late 1980s and mid-1990s was a booming time of discovery for the field of genetics. As researchers vied to identify novel genes, the protein structure and genetic sequence of type IV collagen emerged, providing insight into the etiology of Alport syndrome (Butkowski et al., 1987; Gunwar et al., 1990; Hostikka et al., 1990; Morrison et al., 1991; Saus et al., 1988). This was closely followed by the characterization of PKD1 and PKD2, providing insight into the cause of the most commonly inherited kidney disease, autosomal dominant polycystic kidney disease (ADPKD) (Hughes et al., 1995; International Polycystic Kidney Disease Consortium 1995; Mochizuki et al. 1996). Reports of newly discovered genes and proteins associated with kidney disorders occurred at a breakneck pace throughout the late 1990s and 2000s (Higgs et al., 2005; Honda et al., 1998; Kestilä et al., 1998; Ward et al., 2002).
With technological advancements like next generation sequencing, we continue to see novel genes identified for disorders such as focal segmental glomerulosclerosis (FSGS), congenital anomalies of the kidney and urinary tract, and polycystic kidney disease (Boyer et al., 2013; Bullich et al., 2014; Heidet et al., 2017; Lu et al., 2017). The rise in accessibility and utilization of genetic testing for patients with kidney disease has broadened our understanding of disease phenotypes, such as atypical presentations of Alport syndrome or ADPKD, with significant implications for medical management (Cornec-Le Gall et al., 2018; Malone et al., 2014). For instance, monogenic causes of FSGS/nephrotic syndrome, such as COL4A3/COL4A4, ACTN4, or TRPC6, do not typically respond to standard therapies like steroids and immunosuppression (Büscher et al., 2010; Gribouval et al., 2018). Affected patients experience declining kidney function while new complications may arise due to side effects of these treatments, which can be avoided with early genetic diagnosis. In addition, patients facing endstage kidney disease (ESKD) may wonder if their family members can act as donors, which can be clarified when a pathogenic variant is identified.
Recent developments in therapeutics for inherited kidney diseases present another driving factor in the need for identification and accurate diagnosis for this patient population—not only for accurate recurrence risk, but for personal management of disease (Chebib et al., 2018; Kashtan, 2021; Simonetta et al., 2018). Primary hyperoxaluria, an autosomal recessive disorder of oxalate metabolism characterized by painful kidney stones and ESKD, is now counted among the few conditions with available gene therapy (Keam & Scott, 2021).
With this rapidly evolving landscape, the need for genetic counselors to enter this space has never been more critical. The NSGC Renal Genetics Special Interest Group was created to meet this need. Our growing community has roughly equal representation from clinical and laboratory genetic counselors. Most members have opportunities for students to shadow or to complete elective rotations, and we are actively working on educational outreach initiatives to ensure that students and practicing genetic counselors alike are aware of the potential for an exciting and rewarding career in renal genetics.
References
Boyer, O. et al. Journal of the American Society of Nephrology (2013).
Bullich, G. et al. European Journal of Human Genetics (2014).
Büscher, A. K. et al. Clinical Journal of the American Society of Nephrology (2010).
Butkowski, R. J. et al. Journal of Biological Chemistry (1987).
Chebib, F. T. et al. Journal of the American Society of Nephrology (2018).
Cornec-Le Gall, E. et al. American Journal of Human Genetics (2018).
Gribouval, O. et al. Kidney International (2018).
Gunwar, S. et al. Journal of Biological Chemistry (1990).
Heidet, L. et al. Journal of the American Society of Nephrology (2017).
Higgs, H. N. et al. Molecular Biology of the Cell (2005).
Honda, K. et al. Journal of Cell Biology (1998).
Hostikka, S. L. et al. Proceedings of the National Academy of Sciences (1990).
Hughes, J. et al. Nature Genetics (1995).
Kashtan C. E. American Journal of Kidney Diseases (2021).
Kestilä, M. et al. Molecular Cell (1998).
Lu, H. et al. Nature Genetics (2017).
Malone, A. F. et al., Kidney International (2014).
Mochizuki, T. et al., Science (1996).
Morrison, K. E. et al., Journal of Biological Chemistry (1991).
International Polycstic Kidney Disease Consortium, Cell (1995).
Saus, J. et al., Journal of Biological Chemistry (1988).
Scott, L. J., & Keam, S. J. Drugs (2021).
Simonetta, I. et al., Current Gene Therapy (2018).
Ward, C. J. et al., Nature Genetics (2002).
Mary-Beth Roberts, MS, CGC MS, CGC is a general/pediatric genetic counselor at the Renal Genetics Clinic at the Cleveland Clinic. She is co-founder and co-chair of the Renal Genetics Special Interest Group and is involved in various initiatives promoting this new and growing specialty.