TY - JOUR
T1 - Clinical Pregenetic Screening for Stroke Monogenic Diseases
T2 - Results From Lombardia GENS Registry
AU - Bersano, Anna
AU - Markus, Hugh Stephen
AU - Quaglini, Silvana
AU - Arbustini, Eloisa
AU - Lanfranconi, Silvia
AU - Micieli, Giuseppe
AU - Boncoraglio, Giorgio B
AU - Taroni, Franco
AU - Gellera, Cinzia
AU - Baratta, Silvia
AU - Penco, Silvana
AU - Mosca, Lorena
AU - Grasso, Maurizia
AU - Carrera, Paola
AU - Ferrari, Maurizio
AU - Cereda, Cristina
AU - Grieco, Gaetano
AU - Corti, Stefania
AU - Ronchi, Dario
AU - Bassi, Maria Teresa
AU - Obici, Laura
AU - Parati, Eugenio A
AU - Pezzini, Alessando
AU - De Lodovici, Maria Luisa
AU - Verrengia, Elena P.
AU - Bono, Giorgio
AU - Mazucchelli, Francesca
AU - Zarcone, Davide
AU - Calloni, Maria Vittoria
AU - Perrone, Patrizia
AU - Bordo, Bianca Maria
AU - Colombo, Antonio
AU - Padovani, Alessandro
AU - Cavallini, Anna Maria
AU - Beretta, Simone
AU - Ferrarese, Carlo
AU - Motto, Cristina
AU - Agostoni, Elio
AU - Molini, Graziella
AU - Sasanelli, Francesco
AU - Corato, Manuel
AU - Marcheselli, Simona
AU - Sessa, Maria
AU - Comi, Giancarlo
AU - Checcarelli, Nicoletta
AU - Guidotti, Mario
AU - Uccellini, Davide
AU - Merlini, Giampaolo
AU - Comi, Giacomo Pietro
AU - Vitali, Paolo
AU - Lombardia GENS Group
N1 - © 2016 American Heart Association, Inc.
PY - 2016/7
Y1 - 2016/7
N2 - BACKGROUND AND PURPOSE: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected diseaseMETHODS: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis.RESULTS: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease.CONCLUSIONS: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.
AB - BACKGROUND AND PURPOSE: Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected diseaseMETHODS: We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis.RESULTS: In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease.CONCLUSIONS: In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.
KW - Journal Article
U2 - 10.1161/STROKEAHA.115.012281
DO - 10.1161/STROKEAHA.115.012281
M3 - Article
C2 - 27245348
VL - 47
SP - 1702
EP - 1709
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 7
ER -