NM_000311.4(PRNP):c.478C>T (p.Gln160Ter) AND CEREBRAL AMYLOID ANGIOPATHY, PRNP-RELATED

Clinical significance:Pathogenic (Last evaluated: Apr 1, 2011)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000074470.14

Allele description [Variation Report for NM_000311.4(PRNP):c.478C>T (p.Gln160Ter)]

NM_000311.4(PRNP):c.478C>T (p.Gln160Ter)

Gene:
PRNP:prion protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20p13
Genomic location:
Preferred name:
NM_000311.4(PRNP):c.478C>T (p.Gln160Ter)
HGVS:
  • NC_000020.11:g.4699698C>T
  • NG_009087.1:g.18548C>T
  • NM_000311.4:c.478C>T
  • NM_001271561.1:c.*167C>T
  • NP_000302.1:p.Gln160Ter
  • NC_000020.10:g.4680344C>T
  • NM_000311.3:c.478C>T
Protein change:
Q160*; GLN160TER
Links:
OMIM: 176640.0032; dbSNP: 80356711
NCBI 1000 Genomes Browser:
rs80356711
Molecular consequence:
  • NM_001271561.1:c.*167C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000311.4:c.478C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
CEREBRAL AMYLOID ANGIOPATHY, PRNP-RELATED
Identifiers:
MedGen: CN181778

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000108509OMIMno assertion criteria providedPathogenic
(Apr 1, 2011)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Familial prion disease with Alzheimer disease-like tau pathology and clinical phenotype.

Jayadev S, Nochlin D, Poorkaj P, Steinbart EJ, Mastrianni JA, Montine TJ, Ghetti B, Schellenberg GD, Bird TD, Leverenz JB.

Ann Neurol. 2011 Apr;69(4):712-20. doi: 10.1002/ana.22264. Epub 2011 Mar 17.

PubMed [citation]
PMID:
21416485
PMCID:
PMC3114566

Details of each submission

From OMIM, SCV000108509.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a woman with onset of progressive memory impairment and depression beginning at age 39 years and resulting in death at age 47 (see 137440), Jayadev et al. (2011) identified a heterozygous c.527C-T transition in the PRNP gene, resulting in a gln160-to-ter (Q160X) substitution. The patient was heterozygous for M129V (176640.0005). The patient was initially diagnosed with Alzheimer disease (AD; 104300). Neuropathologic examination showed frontotemporal atrophy, severe tau (MAPT; 157140)-immunoreactive neurofibrillary tangles, and amyloid plaques that were immunoreactive to PrP. The prion deposits were immunopositive to residues 90-102, but not to 220-231, consistent with C-terminal truncation. Western blot analysis showed a smear of protease K-resistant PrP, the most prominent of which was 11 kD. PrP-immunoreactive amyloid angiopathy was also observed. There was also immunoreactivity to alpha-synuclein (SNCA; 163890) in the form of Lewy bodies and Lewy neurites. Spongiform changes were not observed. The patient's deceased mother had a history of a similar disorder accompanied by severe chronic diarrhea but with later onset. She was diagnosed with Alzheimer disease, but reexamination of her pathology showed the same abnormalities as observed in her daughter. The mother also carried the Q160X mutation and was homozygous for M129. Jayadev et al. (2011) postulated a link between truncating PRNP mutations and the development of a disorder with a relatively prolonged clinical course and features similar to AD.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2017