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

Autor: Pasquetti D; Section of Genomic Medicine, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Medical Genetics Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Gazzellone A; Section of Genomic Medicine, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Medical Genetics Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Rossi S; Department of Neurosciences, Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Neurology Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Orteschi D; Section of Genomic Medicine, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Medical Genetics Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., L'Erario FF; Section of Genomic Medicine, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Medical Genetics Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Concolino P; Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Minucci A; Departmental Unit of Molecular and Genomic Diagnostics, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Dionisi-Vici C; Division of Metabolic Diseases, Bambino Gesù Children's Hospital IRCCS, 00165 Rome, Italy., Genuardi M; Section of Genomic Medicine, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Medical Genetics Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Silvestri G; Department of Neurosciences, Faculty of Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Neurology Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy., Chiurazzi P; Section of Genomic Medicine, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.; Medical Genetics Unit, Fondazione Policlinico Universitario 'A. Gemelli' IRCCS, 00168 Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2023 Dec 29; Vol. 25 (1). Date of Electronic Publication: 2023 Dec 29.
DOI: 10.3390/ijms25010495
Abstrakt: 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.
Databáze: MEDLINE
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