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

Autor: Ventayol-Guirado M; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain., Torres L; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain.; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain., Asensio-Landa V; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain.; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain., Pérez-Granero Á; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain., Madrid MI; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain., Hernandez-Rodriguez J; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain.; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain., Llull-Alberti MV; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain., Lumbreras J; Pediatrics Department, Hospital Universitari Son Espases, Palma, Spain.; Health Research Institute of the Balearic Islands (IdISBa), Multidisciplinary Pediatric Research Group, Palma, Spain., Escribà S; Pediatrics Department, Hospital Universitari Son Espases, Palma, Spain., Pons M; Pediatrics Department, Hospital Universitari Son Espases, Palma, Spain., Roldan J; Radiology Department, Hospital Universitari Son Espases, Palma, Spain., Martínez-López I; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain.; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain., Heine-Suñer D; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain.; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain., Santos-Simarro F; Health Research Institute of the Balearic Islands (IdISBa), Genomics of Health research group, Palma, Spain.; Hospital Universitari Son Espases, Unit of Molecular Diagnostics and Clinical Genetics, Palma, Spain.
Jazyk: angličtina
Zdroj: American journal of medical genetics. Part A [Am J Med Genet A] 2024 Dec; Vol. 194 (12), pp. e63830. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1002/ajmg.a.63830
Abstrakt: 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.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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