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Original Article
New mutation in the PSEN1 (E120G) gene associated with early onset Alzheimer's disease
Nueva mutación en el gen PSEN1 (E120G) asociada a enfermedad de Alzheimer de inicio precoz
A. Lladóa,
Corresponding author
allado@clinic.ub.es

Author for correspondence.
, R. Sánchez-Vallea, M.J. Reyb, P. Mercadalc, C. Almenard, D. López-Villegase, J. Forteaa, J.L. Molinuevoa
a Unitat d’Alzheimer i altres trastorns cognitius, Servei de Neurologia, ICN, Hospital Clínic de Barcelona, Institut d’Investigació Biomédica August Pi i Sunyer (IDIBAPS), Barcelona, Spain
b Banc de Teixits Neurològics, Universitat de Barcelona/Hospital Clínic, Barcelona, Spain
c Geriatria, Programa de Trastorns Cognitius, Centres Assistencials Emili Mira i López, Santa Coloma de Gramenet, Barcelona, Spain
d Àrea de Psicogeriatria, Hospital Benito Menni, Sant Boi de Llobregat, Barcelona, Spain
e Neurologia, Unitat de Trastorns Cognitius i de la Conducta, Centres Assistencials Emili Mira i López, Santa Coloma de Gramenet, Barcelona, Spain
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe a novel mutation in exon 5 of the presenilin 1 gene &#40;E120G&#41; associated with early-onset autosomal dominant Alzheimer&#39;s disease &#40;AD&#41;&#46;</p> <span class="elsevierStyleSectionTitle">Patient and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The proband was a man who began with memory loss and progressive cognitive decline at the age of 34&#46; His father and his sister suffered from early-onset cognitive decline&#46; The genetic study performed on the blood sample using the single strand conformation polymorphism &#40;SSCP&#41; technique did not detect any abnormality suggestive of the presence of a mutation in <span class="elsevierStyleItalic">PSEN1&#44; PSEN2&#44;</span> and <span class="elsevierStyleItalic">APP</span>&#46; In the last stage of the disease the patient had seizures and gait alteration&#46; He died at the age of 44&#46; Coding exons 3&#8211;12 of <span class="elsevierStyleItalic">PSEN1</span> were studied by direct sequencing using isolated DNA from frozen brain tissue of the proband&#46;</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The neuropathological examination showed the presence of frequent amyloid plaques and neurofi brillary tangles and severe amyloid angiopathy&#46; The direct sequencing of the <span class="elsevierStyleItalic">PSEN1</span> gene disclosed the presence of the E120G mutation&#46;</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">E120G is a novel mutation in <span class="elsevierStyleItalic">PSEN1</span> that probably causes early-onset autosomal dominant AD&#46; Absence of genetic alterations in screening techniques &#40;SSCP&#41; does not rule out the presence of mutations&#46; We recommend direct sequencing for the genetic study of patients with early-onset autosomal dominant AD&#46;</p>"
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        "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir una nueva mutaci&#243;n en el ex&#243;n 5 del gen <span class="elsevierStyleItalic">PSEN1</span> &#40;E120G&#41; asociada a enfermedad de Alzheimer &#40;EA&#41; de inicio precoz y patr&#243;n de herencia autos&#243;mico dominante&#46;</p> <span class="elsevierStyleSectionTitle">Paciente y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El probando era un var&#243;n en el que se inici&#243; la enfermedad a los 34 a&#241;os con problemas de memoria y deterioro cognitivo progresivo&#46; Su padre y una hermana presentaron deterioro cognitivo de inicio precoz&#46; El estudio gen&#233;tico por <span class="elsevierStyleItalic">single strand conformation polymorphism</span> &#40;SSCP&#41; de una muestra sangu&#237;nea del probando no detect&#243; anormalidades que indicaran mutaciones en <span class="elsevierStyleItalic">PSEN1&#44; PSEN2</span> y <span class="elsevierStyleItalic">APP</span>&#46; En los estadios finales de la enfermedad&#44; el paciente present&#243; crisis epil&#233;pticas y alteraci&#243;n de la marcha&#46; El paciente falleci&#243; a los 44 a&#241;os&#46; Los exones 3&#8211;12 del gen <span class="elsevierStyleItalic">PSEN1</span> fueron analizados por secuenciaci&#243;n directa utilizando ADN aislado del tejido cerebral congelado del probando&#46;</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">El examen neuropatol&#243;gico revel&#243; abundantes placas seniles y ovillos neurofibrilares&#44; junto con una angiopat&#237;a amiloidea severa&#46; El nuevo estudio gen&#233;tico del gen <span class="elsevierStyleItalic">PSEN1</span> realizado mediante secuenciaci&#243;n directa detect&#243; la mutaci&#243;n E120G&#46;</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">E120G es una nueva mutaci&#243;n en <span class="elsevierStyleItalic">PSEN1&#44;</span> probable causa de EA de inicio precoz con patr&#243;n autos&#243;mico dominante&#46; La ausencia de mutaciones en estudios gen&#233;ticos de cribado &#40;SSCP&#41; no descarta que haya mutaciones&#46; Se recomienda el estudio gen&#233;tico mediante secuenciaci&#243;n directa en los casos de EA de inicio precoz y patr&#243;n de herencia autos&#243;mico dominante&#46;</p>"
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ISSN: 21735808
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