PSEN1 and PRNP Gene Mutations Co-occurrence Makes Onset Very Early in a Family with FTD Phenotype

Bernardi, Livia; Anfossi, Maria; Gallo, Maura; Geracitano, Silvana; Colao, Rosanna; Puccio, Gianfranco; Curcio, Sabrina A.M.; Frangipane, Francesca; Mirabelli, Maria; Clodomiro, Alessandra; Lorenzo, Raffaele Di; Smirne, Nicoletta; Maletta, Raffaele; Iapaolo, David; Bruni, Amalia C.

doi:10.3233/jad-2011-101890

Cited by 8 publications

(3 citation statements)

References 25 publications

(31 reference statements)

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“…Molecular function of all genes was retrieved from the gene bank of The National Center for Biotechnology Information (NCBI, U.S. National Library of Medicine, Bethesda MD, USA). Besides these genes that were primarily associated with FTD, mutations in presenilin-1, which are causative of familial AD, have also been associated with a clinical FTD syndrome (Bernardi et al, 2011).…”

Section: Molecular Genetic Studies In Frontotemporal Dementiamentioning

confidence: 99%

A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia

Nascimento

Nunes

Rodriguez

et al. 2019

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Mental disorders are highly prevalent and important causes of medical burden worldwide. Cooccurrence of neurological and psychiatric symptoms are observed among mental disorders, representing a challenge for their differential diagnosis. Psychiatrists and neurologists have faced challenges in diagnosing old adults presenting behavioral changes. This is the case for early frontotemporal dementia (FTD) and bipolar disorder. In its initial stages, FTD is characterized by behavioral or language disturbances in the absence of cognitive symptoms. Consequently, patients with the behavioral subtype of FTD (bv-FTD) can be initially misdiagnosed as having a psychiatric disorder, typically major depression disorder (MDD) or bipolar disorder (BD). Bipolar disorder is associated with a higher risk of dementia in older adults and with cognitive impairment, where a subset of patients presents a neuroprogressive pattern during the disease course. No mendelian mutations were identified in BD, whereas three major genetic causes of FTD have been identified. Clinical similarities between BD and bv-FTD raise the question whether common molecular pathways might explain shared clinical symptoms. Here, we reviewed existing data on clinical and molecular similarities between BD and FTD to propose biological pathways that can be further investigated as common or specific markers of BD and FTD.

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Section: Molecular Genetic Studies In Frontotemporal Dementiamentioning

confidence: 99%

A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia

Nascimento

Nunes

Rodriguez

et al. 2019

Progress in Neuro-Psychopharmacology and Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…Trisomy21/myotonic dystrophy (DM1) [17] No Friedreich's Ataxia/NF1 [18] No CMT1A/CMTX1 [19] Yes CMT1A/myotonic dystrophy (DM1) [19] Yes HNPP/adrenomyeloneuropathy [19] Yes SCA6/EA2 ⁎ Yes PSEN1 (FAD)/PRNP [20] Yes HD/SCA10 (This report) Yes…”

Section: Discussionmentioning

confidence: 99%

The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease

Roxburgh

Smith

Lim³

et al. 2013

Journal of the Neurological Sciences

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“…At least 30 pathogenic mutations have been described for the prion gene ( PRNP ; http://www.federationofscientists.org/pmpanels/TSE/Priprogene.asp ), which could also be involved in different disease phenotypes, such as Creutzfeldt–Jakob disease, familial fatal insomnia, Gerstmann–Straussler–Scheinker disease, or kuru. 4 Pathological similarities were found between AD and prion disease, as neurodegenerative diseases may be based on the aggregation of abnormal proteins. The main signs of AD, cerebral deposits of amyloid plaques, and aggregated tau fibrils could also be present in prion diseases.…”

Section: Introductionmentioning

confidence: 99%

Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family

Ch’ng¹,

An²,

Bae³

et al. 2015

NDT

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Alzheimer’s disease (AD) is the most common form of dementia, which can be categorized into two main forms: early onset AD and late onset AD. The genetic background of early onset AD is well understood, and three genes, the APP, PSEN1, and PSEN2 have been identified as causative genes. In the current study, we tested three siblings from Malaysia who were diagnosed with early onset dementia, as well as their available family members. The family history was positive as their deceased father was similarly affected. Patients were tested for mutations in APP, PSEN1, PSEN2, and PRNP. A novel variant, E280K, was discovered in exon 8 of PSEN1 in the three siblings. In silico analyses with SIFT, SNAP, and PolyPhen2 prediction tools and three-dimensional modeling were performed, and the results suggested that the mutation is probably a pathogenic variant. Two additional pathogenic mutations were previously been described for codon 280, E280A, and E280G, which could support the importance of the E280 residue in the PS1 protein contributing to the pathogenic nature of E280K. Additional ten family members were screened for the E280K mutation, and all of them were negative. Six of them presented with a variety of neuropsychiatric symptoms, including learning disabilities, epilepsy, and schizophrenia, while four family members were asymptomatic. A novel PRNP G127S mutation was found in a step-niece of the three siblings harboring the PSEN1 E280K mutation. In silico predictions for PRNP G127S mutation suggested that this might be possibly a damaging variant. Additional studies to characterize PRNP G127S would be necessary to further understand the effects of this mutation.

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PSEN1 and PRNP Gene Mutations Co-occurrence Makes Onset Very Early in a Family with FTD Phenotype

Cited by 8 publications

References 25 publications

A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia

A review on shared clinical and molecular mechanisms between bipolar disorder and frontotemporal dementia

The unique co-occurrence of spinocerebellar ataxia type 10 (SCA10) and Huntington disease

Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family

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