NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln) AND Alzheimer disease 3

Clinical significance:Pathogenic (Last evaluated: Jun 15, 2004)
Review status:(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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Based on:: 1 submission [Details]
Record status:: current
Accession:: RCV000019780.28

Allele description [Variation Report for NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln)]

NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln)

Gene:

PSEN1:presenilin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.2

Genomic location:

Preferred name:

NM_000021.4(PSEN1):c.1307C>A (p.Pro436Gln)

HGVS:

NC_000014.9:g.73219192C>A
NG_007386.2:g.87722C>A
NM_000021.4:c.1307C>AMANE SELECT
NM_007318.3:c.1295C>A
NP_000012.1:p.Pro436Gln
NP_015557.2:p.Pro432Gln
LRG_224t1:c.1307C>A
LRG_224:g.87722C>A
LRG_224p1:p.Pro436Gln
NC_000014.8:g.73685900C>A
P49768:p.Pro436Gln

Protein change:

P432Q; PRO436GLN

Links:

UniProtKB: P49768#VAR_006460; OMIM: 104311.0028; dbSNP: rs121917808

NCBI 1000 Genomes Browser:

rs121917808

Molecular consequence:

NM_000021.4:c.1307C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_007318.3:c.1295C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Alzheimer disease 3
Synonyms:: Alzheimer disease early onset type 3; ALZHEIMER DISEASE, FAMILIAL, 3
Identifiers:: MONDO: MONDO:0011913; MedGen: C1843013; Orphanet: 1020; OMIM: 607822

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000040078	OMIM	no assertion criteria provided	Pathogenic (Jun 15, 2004)	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 15115757, 9831473

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000040078

OMIM

no assertion criteria provided

Pathogenic
(Jun 15, 2004)

unknown

literature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

Help

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Somatic and germline mosaicism in sporadic early-onset Alzheimer's disease.

Beck JA, Poulter M, Campbell TA, Uphill JB, Adamson G, Geddes JF, Revesz T, Davis MB, Wood NW, Collinge J, Tabrizi SJ.

Hum Mol Genet. 2004 Jun 15;13(12):1219-24. Epub 2004 Apr 28.

PubMed [citation]

PMID:: 15115757

Two novel presenilin-1 mutations (Ser169Leu and Pro436Gln) associated with very early onset Alzheimer's disease.

Taddei K, Kwok JB, Kril JJ, Halliday GM, Creasey H, Hallupp M, Fisher C, Brooks WS, Chung C, Andrews C, Masters CL, Schofield PR, Martins RN.

Neuroreport. 1998 Oct 5;9(14):3335-9.

PubMed [citation]

PMID:: 9831473

Details of each submission

From OMIM, SCV000040078.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Beck et al. (2004) reported a patient with sporadic early-onset Alzheimer disease (AD3; 607822) who was a somatic mosaic for a 71111C-A transversion in exon 12 of the PSEN1 gene. The mutation, which had been described by Taddei et al. (1998), was predicted to result in substitution of glutamine at proline-436 (P436Q). The index patient presented at age 52 years with a 10-year history of progressive parkinsonian syndrome, spastic paraparesis, and dementia; she died 6 years later. The degree of mosaicism was 8% in peripheral lymphocytes and 14% in the cerebral cortex of the index patient. Her daughter, who presented at age 27 years with progressive cerebellar syndrome, spastic paraparesis, and dementia, was heterozygous for the mutation; she died 12 years after diagnosis. The authors hypothesized that mosaicism may be an important mechanism in the etiology of sporadic AD and other apparently sporadic neurodegenerative diseases such as Parkinson disease (see 168601), motor neuron disease, and Creutzfeldt-Jakob disease (123400).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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