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NM_000311.5(PRNP):c.560A>G (p.His187Arg) AND Gerstmann-Straussler-Scheinker syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 12, 2005
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000014353.25

Allele description [Variation Report for NM_000311.5(PRNP):c.560A>G (p.His187Arg)]

NM_000311.5(PRNP):c.560A>G (p.His187Arg)

Gene:
PRNP:prion protein [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20p13
Genomic location:
Preferred name:
NM_000311.5(PRNP):c.560A>G (p.His187Arg)
HGVS:
  • NC_000020.11:g.4699780A>G
  • NG_009087.1:g.18630A>G
  • NM_000311.5:c.560A>GMANE SELECT
  • NM_001080121.3:c.560A>G
  • NM_001080122.3:c.560A>G
  • NM_001080123.3:c.560A>G
  • NM_001271561.3:c.*249A>G
  • NM_183079.4:c.560A>G
  • NP_000302.1:p.His187Arg
  • NP_001073590.1:p.His187Arg
  • NP_001073591.1:p.His187Arg
  • NP_001073592.1:p.His187Arg
  • NP_898902.1:p.His187Arg
  • NC_000020.10:g.4680426A>G
  • P04156:p.His187Arg
Protein change:
H187R; HIS187ARG
Links:
UniProtKB: P04156#VAR_008746; OMIM: 176640.0024; dbSNP: rs74315413
NCBI 1000 Genomes Browser:
rs74315413
Molecular consequence:
  • NM_001271561.3:c.*249A>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000311.5:c.560A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080121.3:c.560A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080122.3:c.560A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001080123.3:c.560A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_183079.4:c.560A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Gerstmann-Straussler-Scheinker syndrome (GSD)
Synonyms:
GERSTMANN-STRAUSSLER DISEASE; CEREBELLAR ATAXIA, PROGRESSIVE DEMENTIA, AND AMYLOID DEPOSITS IN CNS; PRION DEMENTIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007656; MedGen: C0017495; Orphanet: 356; OMIM: 137440

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000034602OMIM
no assertion criteria provided
Pathogenic
(Apr 12, 2005) 		germlineliterature only

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Novel PRNP sequence variant associated with familial encephalopathy.

Cervenáková L, Buetefisch C, Lee HS, Taller I, Stone G, Gibbs CJ Jr, Brown P, Hallett M, Goldfarb LG.

Am J Med Genet. 1999 Dec 15;88(6):653-6.

PubMed [citation]
PMID:
10581485

Inherited prion encephalopathy associated with the novel PRNP H187R mutation: a clinical study.

Bütefisch CM, Gambetti P, Cervenakova L, Park KY, Hallett M, Goldfarb LG.

Neurology. 2000 Aug 22;55(4):517-22.

PubMed [citation]
PMID:
10953183
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000034602.7

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (3)

Description

In affected individuals from an American family of English origin with a prion disease clinically similar to Gerstmann-Straussler disease (GSD; 137440), Cervenakova et al. (1999) and Butefisch et al. (2000) identified an A-to-G transition in the PRNP gene, resulting in a his187-to-arg (H187R) substitution in the third alpha-helical segment of the protein. Six unaffected family members did not have the mutation. Median age at disease onset was 42 years (range 33 to 50 years), characterized by ataxic gait, dysarthria, behavioral abnormalities, and cognitive decline. All of the patients had cerebellar atrophy, 3 developed myoclonic jerks, and 2 developed seizures. Only 1 patient showed intermittent triphasic periodic synchronous waves on EEG. Median disease duration was 12 years. Brain biopsy of 1 patient showed round or elongated PrP 'curly' granular deposits in the cortex without spongiform changes. No autopsies were performed.

Hall et al. (2005) identified the H187R mutation in affected members of a family with dementia, cerebellar signs, and extrapyramidal signs. Four patients developed neuropsychiatric symptoms (see 606688) in childhood or adolescence, including kleptomania, pyromania, and impulsivity. Age at onset of dementia ranged from 20 to 44 years. Neuropathologic examination of 4 patients showed moderate to severe cerebral atrophy, without other distinctive features.

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

Last Updated: Feb 13, 2023