EXPANDING THE GENES IMPLICATED IN POLYCYSTIC KIDNEY DISEASE
Gemma Scholes1, Yael Prawer1, Jessica Ryan1, Kunal Verma1,2, Kushani Jayasinghe1,3 1Monash Health, Melbourne, Victoria, Australia2Monash Heart, Melbourne, Victoria, Australia3Monash University, Melbourne, Victoria, Australia
Abstract
Background: Genetic kidney diseases (GKD) account for at least 10% of kidney failure. Recent changes to Australian Medicare reimbursements now allow Nephrologists to order genomic testing, meaning they will need to keep abreast of the evolving field of genetics.
Case: A 34-year-old female with a clinical diagnosis of autosomal recessive polycystic kidney disease (ARPKD) following presentation with renal failure in infancy.
The case was referred to our genetics clinic for reproductive counselling. Based on the presumptive diagnosis of ARPKD, she was advised that her children were likely to be healthy carriers. Exome testing was performed (cystic disease super-panel). No pathogenic variants were identified; however a heterozygous variant of uncertain significance was found in NEK8 (NM_178170:p.Arg45Trp), a gene previously thought only to cause disease via recessive inheritance. Given the high index of suspicion of a genetic cause, further analysis was requested after international collaboration. This variant was then reclassified as likely-pathogenic result, based on recent data suggesting that this gene was also implicated in dominant disease. This finding had significant reproductive implications for our case, as her future children would now be at 50% risk of inheriting the condition. Consequently, she proceeded with pre-implantation genetic testing to avoid passing on the NEK8 variant to future children.
Conclusion: This case highlights the importance of an accurate genomic diagnosis. One of the challenges of GKD is the constantly expanding phenotypic spectra, as well as the growing list of disease-causing genes. As more testing for cystic kidney disease is likely to occur in the nephrology clinic, this case highlights the importance of multidisciplinary collaboration, and consideration of further analyses when initial genomic testing is negative despite high clinical suspicion.
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