Diagnostic Approach of Early-Onset Dementia with Negative Family History: Implications from Two Cases of Early-Onset Alzheimer’s Disease with De Novo PSEN1 Mutation
Restricted accessResearch articleFirst published online March 29, 2019
Diagnostic Approach of Early-Onset Dementia with Negative Family History: Implications from Two Cases of Early-Onset Alzheimer’s Disease with De Novo PSEN1 Mutation
For early-onset Alzheimer’s disease (EOAD) cases with unclear family history, most cases are sporadic. Some cases are positive in genetic findings, that is, either incomplete penetrance or de novo mutation. We aimed to focus on EOAD cases with de novo mutations. Case reports and literature review were performed. The implication for diagnostic approach of early-onset dementia with negative family history was developed. We reported two Chinese EOAD cases with de novo mutations. The genotype PSEN1 G206S appeared to correlate with the phenotype of EOAD with pure cognitive problems. The second case had a PSEN1 M233V mutation with an earlier age of onset of 25 with cognitive decline, parkinsonism, and epilepsy. Although EOAD due to de novo mutations is not common, it should be considered in patients with a phenotype of progressive cognitive decline and amyloid positivity on PET or CSF analysis.
DumanchinC, BriceA, CampionD, HannequinD, MartinC, MoreauV, AgidY, MartinezM, Clerget-DarpouxF, FrebourgT (1998) De novo presenilin 1 mutations are rare in clinically sporadic, early onset Alzheimer’s disease cases. French Alzheimer’s Disease Study Group. J Med Genet35, 672–673.
2.
CarecchioM, PicilloM, VallettaL, EliaAE, HaackTB, CozzolinoA, VitaleA, GaravagliaB, IusoA, BagellaCF, PappatáS, BaroneP, ProkischH, RomitoL, TirantiV (2017) Rare causes of early-onset dystonia-parkinsonism with cognitive impairment: A de novo PSEN-1 mutation. Neurogenetics18, 175–178.
3.
LanoiseléeHM, NicolasG, WallonD, Rovelet-LecruxA, LacourM, RousseauS, RichardAC, PasquierF, Rollin-SillaireA, MartinaudO, Quillard-MuraineM, de la SayetteV, Boutoleau-BretonniereC, Etcharry-BouyxF, ChauviréV, SarazinM, le BerI, EpelbaumS, JonveauxT, RouaudO, CeccaldiM, FélicianO, GodefroyO, FormaglioM, CroisileB, AuriacombeS, ChamardL, VincentJL, SauvéeM, Marelli-TosiC, GabelleA, OzsancakC, ParienteJ, PaquetC, HannequinD, CampionD; collaborators of the CNR-MAJ project (2017) APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med14, e1002270.
4.
LouF, LuoX, LiM, RenY, HeZ (2017) Very early-onset sporadic Alzheimer’s disease with a de novo mutation in the PSEN1 gene. Neurobiol Aging53, 193.e1–193.e5.
5.
BagyinszkyE, ParkSA, KimHJ, ChoiSH, AnSS, KimSY (2016) SEN1 L226F mutation in a patient with early-onset Alzheimer’s disease in Korea. Clin Interv Aging11, 1433–1440.
6.
GolanMP, StyczyńskaM, JóźwiakK, WaleckiJ, MaruszakA, PniewskiJ, LugiewiczR, FilipekS, ZekanowskiC, BarcikowskaM (2007) Early-onset Alzheimer’s disease with a de novo mutation in the presenilin 1 gene. Exp Neurol208, 264–268.
La BellaV, LiguoriM, CittadellaR, SettipaniN, PiccoliT, MannaI, QuattroneA, PiccoliF (2004) A novel mutation (Thr116Ile) in the presenilin 1 gene in a patient with early-onset Alzheimer’s disease. Eur J Neurol11, 521–524.
9.
PortetF, DauvilliersY, CampionD, RauxG, HauwJJ, Lyon-CaenO, CamuW, TouchonJ (2003) Very early onset AD with a de novo mutation in the presenilin 1 gene (Met 233 Leu). Neurology61, 1136–1137.
10.
CrabtreeT, AltaanS, TarikA (2016) Early-onset dementia in type 1 diabetes mellitus. Pract Diabetes33, 133–134.
11.
RossorMN, FoxNC, BeckJ, CampbellTC, CollingeJ (1996) Incomplete penetrance of familial Alzheimer’s disease in a pedigree with a novel presenilin-1 gene mutation. Lancet347, 1560.
12.
RogaevaEA, FafelKC, SongYQ, MedeirosH, SatoC, LiangY, RichardE, RogaevEI, FrommeltP, SadovnickAD, MeschinoW, RockwoodK, BossMA, MayeuxR, St George-HyslopP (2001) Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations. Neurology57, 621–625.
13.
RauxG, Guyant-MaréchalL, MartinC, BouJ, PenetC, BriceA, HannequinD, FrebourgT, CampionD (2005) Molecular diagnosis of autosomal dominant early onset Alzheimer’s disease: An update. J Med Genet42, 793–795.
14.
ParkHK, NaDL, LeeJH, KimJW, KiCS (2008) Identification of PSEN1 and APP gene mutations in Korean patients with early-onset Alzheimer’s disease. J Korean Med Sci23, 213–217.
15.
HouldenH, CrookR, DolanRJ, McLaughlinJ, ReveszT, HardyJ (2001) A novel presenilin mutation (M233V) causing very early onset Alzheimer’s disease with Lewy bodies. Neurosci Lett313, 93–95.
16.
ReveszT, McLaughlinJL, RossorMN, LantosPL (1997) Pathology of familial Alzheimer’s disease with Lewy bodies. J Neural Transm Suppl51, 121–135.
17.
LiuJ, WangLN, WuLY, WangYP (2016) Treatment of epilepsy for people with Alzheimer’s disease. Cochrane Database Syst Rev11, CD011922.
18.
Appel-CresswellS, GuellaI, LehmanA, FotiD, FarrerMJ (2018) PSEN1 p.Met233Val in a complex neurodegenerative movement and neuropsychiatric disorder. J Mov Disord11, 45–48.
19.
LiN, LiuK, QiuY, RenZ, DaiR, DengY, QingH (2016) Effect of presenilin mutations on APP cleavage; insights into the pathogenesis of FAD. Front Aging Neurosci8, 51.
