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Rudenskaya G.E.

Bochkov Research Centre for Medical Genetics

Petukhova M.S.

Research Centre for Medical Genetics

Zabnenkova V.V.

Research Centre for Medical Genetics

Cherevatova T.B.

Research Centre for Medical Genetics

Ryzhkova O.P.

Bochkov Research Centre for Medical Genetics

Early-onset familial Alzheimer’s disease with spastic paraparesis associated with PSEN1 gene

Authors:

Rudenskaya G.E., Petukhova M.S., Zabnenkova V.V., Cherevatova T.B., Ryzhkova O.P.

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Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(11): 120‑127

DOI: 10.17116/jnevro2023123111120

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Rudenskaya GE, Petukhova MS, Zabnenkova VV, Cherevatova TB, Ryzhkova OP. Early-onset familial Alzheimer’s disease with spastic paraparesis associated with PSEN1 gene. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(11):120‑127. (In Russ.)
https://doi.org/10.17116/jnevro2023123111120

 
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A familial case of a rare autosomal dominant Alzheimer’s disease (AD), related to PSEN1 gene (AD3, OMIM 607822), differing from common multifactorial form by earlier onset and, in part of cases, by accompanying neurological signs, spastic paraparesis particularly, is presented. The first sign in a female proband and in her son was paraparesis manifested at the age of 29 and 21 years, respectively. Cognitive disturbances developed soon; the former diagnosis was hereditary spastic paraplegia with cognitive impairment, In the proband examined in 2008 at 33 years old the diagnosis was not established. In the son examined in 2022 at 27 years old whole-exome sequencing detected a novel PSEN1 missense mutation p.Thr421Ala. The mutation was confirmed by Sanger sequencing in him, found out in the proband (who was severely disabled by that time) and excluded in her unaffected mother. Except for different age of onset, AD3 in two patients was similar, though in whole it is variable, also in relatives. The variability and rareness of the disease hampers clinical diagnostics. Massive parallel sequencing is a most reliable diagnostic method.

Keywords:

early-onset familial Alzheimer’s disease
spastic paraparesis
PSEN1 gene
novel mutation
whole-exome sequencing

Authors:

Rudenskaya G.E.

Bochkov Research Centre for Medical Genetics

Petukhova M.S.

Research Centre for Medical Genetics

Zabnenkova V.V.

Research Centre for Medical Genetics

Cherevatova T.B.

Research Centre for Medical Genetics

Ryzhkova O.P.

Bochkov Research Centre for Medical Genetics

Received:

20.06.2023

Accepted:

18.08.2023

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