Abstract
We report a 54-year-old man who was admitted to the hospital because of acute neurological symptoms due to a cerebral haemorrhage. Postmortem brain examination revealed a lobar haemorrhage and advanced AD neuropathologic changes associated with severe cerebral amyloid angiopathy. Genetic study evidenced the presence of a large APP locus duplication (APPdup) in the patient and a PSEN1 p.E318G polymorphism in him and his older asymptomatic sibling. The APPdup spanned 14.5 Mb and blocks of segmental duplications were detected in the breakpoints. We propose the replication-based mechanism of Fork Stalling Template Switching (FoSTeS) to explain this APPdup rearrangement.
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Acknowledgments
We thank brain donors and relatives’ generous brain donation for research. We are indebted to the Neurological Tissue Bank of the IDIBAPS Biobank, Barcelona, for sample and data procurement. This work was developed at the Centre de Recerca Biomèdica CELLEX, Barcelona, Spain. We thank the support of the Spanish Ministry of Economy and Competitiveness for grants to Dr. Albert Lladó (PI11/00234. ISCIII. Cofinancia FEDER. Unión Europea. Otra manera de hacer Europa), to Dr. José Luis Molinuevo (Consolider CSD2010-00045) and to Dr. Raquel Sánchez-Valle (FIS12/00013). Dr. Ellen Gelpi is partially supported by the Spanish Ministry of Economy and Competitiveness, programa PTA 2011.
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Lladó, A., Grau-Rivera, O., Sánchez-Valle, R. et al. Large APP locus duplication in a sporadic case of cerebral haemorrhage. Neurogenetics 15, 145–149 (2014). https://doi.org/10.1007/s10048-014-0395-z
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DOI: https://doi.org/10.1007/s10048-014-0395-z