Triple Genetic Diagnosis in a Patient with Late-Onset Leukodystrophy and Mild Intellectual Disability

Domizia Pasquetti, Annalisa Gazzellone, S Rossi, D Orteschi, Federica Francesca L'Erario, Paola Concolino, Angelo Minucci, C Dionisi-Vici, Maurizio Genuardi, Gabriella Silvestri, Pietro Chiurazzi

Risultato della ricerca: Contributo in rivistaArticolo in rivista


We describe the complex case of a 44-year-old man with polycystic kidney disease, mild cognitive impairment, and tremors in the upper limbs. Brain MRI showed lesions compatible with leukodystrophy. The diagnostic process, which included clinical exome sequencing (CES) and chromosomal microarray analysis (CMA), revealed a triple diagnosis: autosomal dominant polycystic kidney disease (ADPKD) due to a pathogenic variant, c.2152C>T-p.(Gln718Ter), in the PKD1 gene; late-onset phenylketonuria due to the presence of two missense variants, c.842C>T-p.(Pro281Leu) and c.143T>C-p.(Leu48Ser) in the PAH gene; and a 915 Kb duplication on chromosome 15. Few patients with multiple concurrent genetic diagnoses are reported in the literature; in this ADPKD patient, genome-wide analysis allowed for the diagnosis of adult-onset phenylketonuria (which would have otherwise gone unnoticed) and a 15q11.2 duplication responsible for cognitive and behavioral impairment with incomplete penetrance. This case underlines the importance of clinical genetics for interpreting complex results obtained by genome-wide techniques, and for diagnosing concurrent late-onset monogenic conditions.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaInternational Journal of Molecular Sciences
Stato di pubblicazionePubblicato - 2023




Entra nei temi di ricerca di 'Triple Genetic Diagnosis in a Patient with Late-Onset Leukodystrophy and Mild Intellectual Disability'. Insieme formano una fingerprint unica.

Cita questo