Atypical noncontiguous TSC2/PKD1 gene deletions presenting as tuberous sclerosis/polycystic kidney disease contiguous gene syndrome

• Published in: American journal of medical genetics. Part A Vol. 194; no. 12; pp. e63830 - n/a
• Main Authors: Ventayol‐Guirado, Marc, Torres, Laura, Asensio‐Landa, Victor, Pérez‐Granero, Ángeles, Madrid, Maria Isabel, Hernandez‐Rodriguez, Jessica, Llull‐Alberti, Maria Victoria, Lumbreras, Javier, Escribà, Silvia, Pons, Monserrat, Roldan, Jordi, Martínez‐López, Iciar, Heine‐Suñer, Damian, Santos‐Simarro, Fernando
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.12.2024; Wiley Subscription Services, Inc
• Subjects: ADPKD; Chromosome deletion; Chromosome rearrangements; complex genomic rearrangement; Gene deletion; Gene rearrangement; Genetic analysis; germline mutation; Kidney diseases; Polycystic kidney; Polycystic kidney disease 1 protein; polycystin 1; TSC; TSC2 gene; TSC2/PKD1 CGS; Tuberous sclerosis; ADPKD; complex genomic rearrangement; polycystin 1; TSC; germline mutation; TSC2/PKD1 CGS
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63830

Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are genetically distinct disorders typically associated with pathogenic variants in TSC1 and TSC2 for the former and PKD1 and PKD2 for the latter. TSC2 and PKD1 lie adjacent to each other, and large deletions comprising both genes lead to TSC2/PKD1 contiguous gene deletion syndrome (CGS). In this study, we describe a young female patient exhibiting symptoms of TSC2/PKD1 CGS in which genetic analysis disclosed two noncontiguous partial gene deletions in TSC2 and PKD1 that putatively are responsible for the manifestations of the syndrome. Further analysis revealed that both deletions appear to be de novo on the maternal chromosome, presumably with a germline origin. Despite extensive analysis, no maternal chromosomal rearrangement triggering these pathogenic variants was detected. This case elucidates a unique pathogenesis for TSC2/PKD1 CGS, diverging from the common contiguous deletions typically observed, marking the first reported instance of TSC2/PKD1 CGS caused by independent, functionally significant partial gene deletions.