A novel PSEN2 mutation associated with a peculiar phenotype

Background: Mutations of presenilin 2 gene are a rare cause of familial Alzheimer disease (AD).
We describe an Italian family with hereditary dementia associated with a novel mutation in the
presenilin 2 gene.
Methods: Clinical investigations of the diseased subjects; interviews with relatives; studies of
medical records; pedigree analysis; and neuroradiologic, neuropathologic, and molecular genetic
studies were carried out in the pedigree.
Results: Genetic analysis showed a novel PSEN2 A85V mutation present in the proband and in all
analyzed affected members, in a subject presenting with an amnesic mild cognitive impairment,
and in a young, still asymptomatic subject. The proband showed a clinical phenotype indicative of
Lewy body dementia and the neuropathologic examination demonstrated the presence of unusually
abundant and widespread cortical Lewy bodies in addition to the hallmark lesions of AD. Other
affected members exhibited a clinical phenotype typical of AD.
Conclusions: Our findings add complexity to the spectrum of atypical phenotypes associated with
presenilin mutations and should then be taken into account when considering the nosography of
neurodegenerative diseases. They also support previous data that specific mutations of genes
associated with familial Alzheimer disease may influence the presence and extent of Lewy bodies.