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Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer’s disease in Mexican families

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Abstract

The etiology of Alzheimer’s disease (AD) is complex. To date, molecular genetic studies in several families affected with AD have identified three genes associated with highly penetrant early-onset AD: Presenilin 1 (PSEN1), Presenilin 2 (PSEN2) and β-amyloid precursor protein (APP); and one gene (apolipoprotein E) associated with late-onset AD. Molecular analysis of the PSEN1 gene was performed by direct sequencing of genomic DNA. The possible founder effect was investigated analyzing two highly polymorphic microsatellite markers flanking the PSEN1 gene. Twelve unrelated Mexican families with early-onset AD were analyzed. The Ala431Glu mutation in exon 12 of PSEN1 was found in nine (75%) of these families, which segregated showing autosomal dominant inheritance. Because all families bearing the mutation are from the State of Jalisco (located in Western Mexico), a founder effect was hypothesized. Microsatellite haplotype analysis suggested a common ancestor in these nine kindreds. In conclusion, the Ala431Glu mutation is a prevalent cause of early-onset familial Alzheimer’s disease in families from the State of Jalisco, Mexico. Genetic evidence supports that it is a founder mutation descending from a single common ancestor. These findings have important implications for prompt diagnosis and genetic counseling for Mexican patients with familial AD from Jalisco.

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Acknowledgements

This study was partially supported by grant 28664M from CONACYT, Mexico. We thank the patients and family members for participating in the study and S. Ramirez-Jimenez for laboratory technical assistance.

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Authors and Affiliations

  1. Departamento de Neurogenética y Biología Molecular, lnstituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, México D.F., México

    Petra Yescas, Astrid Rasmussen & María Elisa Alonso

  2. Programa de Doctorado en Ciencias Biológicas, Universidad Autónoma Metropolitana, México D.F., México

    Petra Yescas

  3. Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán e Instituto de Investigaciones Biomédicas de la UNAM, México D.F., México

    Adriana Huertas-Vazquez, María Teresa Villarreal-Molina, María Teresa Tusié-Luna & Samuel Canizales-Quinteros

  4. Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana-Xochimilco, México D.F., México

    Marisol López

  5. Departamento de Neurogenética, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez, Insurgentes Sur 3877, Colonia La Fama, Tlalpan, 14269, México D.F., México

    María Elisa Alonso

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  1. Petra Yescas
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  2. Adriana Huertas-Vazquez
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  8. María Elisa Alonso
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Correspondence to María Elisa Alonso.

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Yescas, P., Huertas-Vazquez, A., Villarreal-Molina, M.T. et al. Founder effect for the Ala431Glu mutation of the presenilin 1 gene causing early-onset Alzheimer’s disease in Mexican families. Neurogenetics 7, 195–200 (2006). https://doi.org/10.1007/s10048-006-0043-3

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  • DOI: https://doi.org/10.1007/s10048-006-0043-3

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