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Spastic paraparesis and atypical dementia caused by PSEN1 mutation (P264L), responsible for Alzheimer's disease
  1. M-L Jacquemont1,
  2. D Campion2,
  3. V Hahn3,
  4. C Tallaksen3,4,
  5. T Frebourg2,
  6. A Brice1,3,4,
  7. A Durr1,3,4
  1. 1Département de Génétique Médicale, Cytogénétique et Embryologie, Hôpital de la Salpêtriére, Paris, France
  2. 2INSERM EPI 9906, Faculté de Médecine et de Pharmacie, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides, Rouen, France
  3. 3Fédération de Neurologie, Hôpital de la Salpêtriére, Paris, France
  4. 4INSERM U289, Hôpital de la Salpêtriére, Paris, France
  1. Correspondence to:
 Dr A Durr, Département de Génétique Médicale, Cytogénétique et Embryologie, Hôpital de la Salpêtriére, Paris, France;
 durr{at}ccr.jussieu.fr

https://doi.org/10.1136/jmg.39.2.e2

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    Alzheimer's disease, the most common cause of dementia in later life, is genetically heterogeneous. Mutations in three genes encoding the amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) are responsible for autosomal dominant early onset cases. A few families have been described in which PSEN1 mutations, usually exon 9 deletions, cause progressive dementia associated with spastic paraparesis.1–5 We present a family in which another PSEN1 mutation causes disease that begins with spastic paraparesis and is associated with dementia that is not of the Alzheimer type.

    The index case first presented at the age of 54 with lower back pain and gait difficulties; he was unable to squat unaided and walked with caution. He complained of a memory deficit that he attributed to the Algerian war, 34 years ago. On examination, he had brisk reflexes in all four limbs and normal muscle tone. Blood cell counts, CSF glucose and protein levels, electromyography, and nerve conduction velocity were unremarkable. A lumbar CT scan and cervicothoracic MRI showed no signs of spinal compression. Brain MRI showed mild cortical atrophy.

    One year later, the patient had a bilateral extensor plantar reflex, with clonus of the patella and proximal muscle weakness in the lower limbs. There was no …

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