Targeted re-sequencing in pediatric and perinatal stroke
| Autor: | Laura Banov, Antonella Palmieri, Marta Bertamino, Capra, Sara Uccella, Lino Nobili, Andrea Rossi, Anna Bruna Ronchetti, Alice Grossi, Luca A. Ramenghi, Mariasavina Severino, Marco Pavanello, G. Prato, Roberta Caorsi, Angelo Claudio Molinari, Andrea Moscatelli, Domenico Tortora, Giulia Amico, Francesco Caroli, Carlo Gandolfo, Maja Di Rocco, Isabella Ceccherini, Thea Giacomini, Paolo Moretti, Armando Cama, Sara Signa, Alessandro Rimini, Marta Rusmini |
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| Rok vydání: | 2020 |
| Předmět: |
Collagen Type IV
Male 0301 basic medicine medicine.medical_specialty Adolescent Arteriopathy Magnetic resonance imaging Next-generation sequencing Pediatric stroke Perinatal stroke Porencephaly ABCC6 030105 genetics & heredity 03 medical and health sciences symbols.namesake Internal medicine Genetics medicine Humans Genetic Testing Family history Child Stroke Genetics (clinical) medicine.diagnostic_test biology business.industry Infant Newborn Infant Sequence Analysis DNA General Medicine medicine.disease Phenotype 030104 developmental biology Child Preschool biology.protein Mendelian inheritance symbols Female Multidrug Resistance-Associated Proteins business |
| Zdroj: | European Journal of Medical Genetics. 63:104030 |
| ISSN: | 1769-7212 |
| DOI: | 10.1016/j.ejmg.2020.104030 |
| Popis: | Pediatric and perinatal stroke can present as an early symptom in undiagnosed syndromes characterized by simple Mendelian inheritance. In order to diagnose those patients affected with a monogenic disorder in which an arterial cerebrovascular event or arteriopathy may have preceded any other specific symptom, we aimed to establish and validate a targeted gene panel, and to determine its diagnostic yield and clinical utility. To this end, thirty-eight patients were selected with heterogeneous cryptogenic stroke phenotypes, mostly including multiple and recurrent ischemic or hemorrhagic arterial strokes and porencephalies, variably associated with calcifications, intracranial or systemic steno-occlusive arteriopathies, positive family history, and syndromic conditions. Clinical and neuroradiological data were collected for every patient enrolled in the study, and DNA samples were tested by means of a customized gene panel including 15 genes associated with known genetic diseases related to pediatric stroke. In four patients (10.5%) the analyses unraveled pathogenetic variants in ABCC6 and COL4A1 genes, leading to a definite genetic diagnosis with a great beneficial impact on patients management, while results were null in the remaining patients. These findings suggest a high complexity and variability of the included stroke phenotypes, that could not be fully accounted for by the genes tested in the present study. A wider gene panel or an unbiased genomic approach may be better suited and advisable to explain a greater proportion of pediatric and perinatal stroke events. |
| Databáze: | OpenAIRE |
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