Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation
| العنوان: | Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation |
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| المؤلفون: | Sandro Sorbi, Orso Bugiani, Lorenzo Pinessi, Innocenzo Rainero, Carmine Tomaino, Livia Bernardi, B. Terni, Alfredo Postiglione, Alessandra Clodomiro, Sabina Pappatà, J. F. Foncin, R. Di Lorenzo, N. Abbamondi, Raffaele Maletta, M. Anfossi, L. Nee, Francesca Frangipane, P H St George Hyslop, A. Leotta, M. G. Muraca, Sabrina A.M. Curcio, Graziella Milan, Giorgio Giaccone, Gianfranco Puccio, Elisa Rubino, Amalia C. Bruni, Ekaterina Rogaeva, Silvana Geracitano, Rosanna Colao, Maura Gallo, Maria Grazia Spillantini, Gianluigi Forloni, Maria Mirabelli, Nicoletta Smirne, S Lio |
| المصدر: | Neurology 74 (2010): 798–806. doi:10.1212/WNL.0b013e3181d52785 info:cnr-pdr/source/autori:Bruni AC;Bernardi L;Colao R;Rubino E;Smirne N;Frangipane F;Terni B;Curcio SA;Mirabelli M;Clodomiro A;Di Lorenzo R;Maletta R;Anfossi M;Gallo M;Geracitano S;Tomaino C;Muraca MG;Leotta A;Lio SG;Pinessi L;Rainero I;Sorbi S;Nee L;Milan G;Pappatà S;Postiglione A;Abbamondi N;Forloni G;St George Hyslop P;Rogaeva E;Bugiani O;Giaccone G;Foncin JF;Spillantini MG;Puccio G./titolo:Worldwide distribution of PSEN1 Met146Leu mutation: a large variability for a founder mutation./doi:10.1212%2FWNL.0b013e3181d52785/rivista:Neurology/anno:2010/pagina_da:798/pagina_a:806/intervallo_pagine:798–806/volume:74 |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Alzheimer disease, presenilin 1, Genotype, International Cooperation, Population, Biology, Global Health, PSEN1 mutation, History, 21st Century, Presenilin, History, 17th Century, Methionine, Gene Frequency, Alzheimer Disease, Fluorodeoxyglucose F18, Leucine, Presenilin-1, PSEN1, medicine, Humans, Genetic Predisposition to Disease, Genetic Testing, education, Prefrontal cortex, Family Health, Genetics, Memory Disorders, education.field_of_study, Brain, Articles, Middle Aged, Alzheimer's disease, medicine.disease, founder effect, Phenotype, Dorsolateral prefrontal cortex, medicine.anatomical_structure, Italy, Positron-Emission Tomography, Mutation, Mutation (genetic algorithm), Female, Neurology (clinical), Cognition Disorders |
| الوصف: | Objective: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 ( PSEN1 ) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide. Methods: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 ± 4.8 years) by clinical, neuropsychological, and molecular methodologies. Results: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction. Conclusions: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f79a5059afdc1cd6987baed55d02717Test http://hdl.handle.net/2318/152288Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5f79a5059afdc1cd6987baed55d02717 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |