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Abstract: SA-PO764

Case Report: Mosaic TSC2/PKD1 Contiguous Gene Deletion Syndrome

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic


  • Fryml, Elise, The University of British Columbia, Vancouver, British Columbia, Canada
  • Lanktree, Matthew B., McMaster University, Hamilton, Ontario, Canada

A rare overlap of tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) can occur when large deletions impact the adjacent TSC2 and PKD1 genes, leading to TSC2/PKD1 contiguous gene deletion syndrome. We present a case of TSC2-PKD1 contiguous gene deletion syndrome with somatic mosaicism where initial genetic testing did not identify a pathogenic variant.

Case Description

A 21-year-old female patient was referred to the McMaster Kidney Genetics Clinic with clinical features consistent with TSC, including childhood epilepsy, multiple bilateral brain tubers, angiofibromas, ash leaf lesions, and bilateral kidney cysts. There was no family history of TSC or PKD. In childhood, she was diagnosed with bilateral renal angiomyolipomas (AMLs) on ultrasound. Her most recent creatinine was 0.75 mg/dL with eGFR of 117 ml/ min/1.73m2. Magnetic resonance imaging of the kidneys at age 18 revealed numerous bilateral kidney cysts including complex heterogenous cysts in an atypical lopsided distribution (Mayo class 2) but no evidence of fat containing AML. Clinical genetic testing with capillary sequencing and multiplex ligation-dependent probe amplification (MLPA) for PKD1, PKD2, TSC1, and TSC2 did not identify a responsible pathogenic variant. A follow up cystic kidney disease gene panel was arranged which identified a deletion spanning exons 15-46 of PKD1 and exons 32-42 of TSC2 predicted to be in 35% of the patient’s circulating white blood cells, suggesting somatic mosaicism and a diagnosis of TSC2-PKD1 contiguous gene deletion syndrome.


Through unexpectedly low read depths, next generation sequencing gene panels can identify deletions. However, detection of somatic mosaicism can be challenging as the variant allele frequency can be above the expected 50% for a heterozygous deletion. Patients with somatic variants may present atypically with more subtle phenotypic features than patients with classical pathogenetic variants. Patients with TSC can have small kidney cysts, though their phenotype should be quite clinically distinct from ADPKD. Our case demonstrates an example of mosaic TSC2-PKD1 contiguous gene deletion syndrome and the improved sensitivity for somatic genetic variants with gene panel sequencing over traditional capillary sequencing and MLPA.