Exome sequencing in an Italian family with Alzheimer's disease points to a role for seizure-related gene 6 (SEZ6) rare variant R615H.
Alzheimers Res Ther
; 10(1): 106, 2018 10 12.
Article
in En
| MEDLINE
| ID: mdl-30309378
ABSTRACT
BACKGROUND:
The typical familial form of Alzheimer's disease (FAD) accounts for about 5% of total Alzheimer's disease (AD) cases. Presenilins (PSEN1 and PSEN2) and amyloid-ß (A4) precursor protein (APP) genes carry all reported FAD-linked mutations. However, other genetic loci may be involved in AD. For instance, seizure-related gene 6 (SEZ6) has been reported in brain development and psychiatric disorders and is differentially expressed in the cerebrospinal fluid of AD cases.METHODS:
We describe a targeted exome sequencing analysis of a large Italian kindred with AD, negative for PSEN and APP variants, that indicated the SEZ6 heterozygous mutation R615H is associated with the pathology.RESULTS:
We overexpressed R615H mutation in H4-SW cells, finding a reduction of amyloid peptide Aß(1-42). Sez6 expression decreased with age in a mouse model of AD (3xTG-AD), but independently from transgene expression.CONCLUSIONS:
These results support a role of exome sequencing for disease-associated variant discovery and reinforce available data on SEZ6 in AD models.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Alzheimer Disease
/
Exome Sequencing
/
Nerve Tissue Proteins
Type of study:
Prognostic_studies
Limits:
Adult
/
Aged
/
Aged80
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Alzheimers Res Ther
Year:
2018
Document type:
Article
Affiliation country:
Italy