Case report of homozygous E200D mutation of PRNP in apparently sporadic Creutzfeldt-Jakob disease.
CJD
E200D
Inherited prion disease
PRNP
Prion
Recessive
Journal
BMC neurology
ISSN: 1471-2377
Titre abrégé: BMC Neurol
Pays: England
ID NLM: 100968555
Informations de publication
Date de publication:
28 Jun 2021
28 Jun 2021
Historique:
received:
19
11
2020
accepted:
09
06
2021
entrez:
29
6
2021
pubmed:
30
6
2021
medline:
10
7
2021
Statut:
epublish
Résumé
Inherited prion diseases are rare autosomal dominant disorders associated with diverse clinical presentations. All are associated with mutation of the gene that encodes prion protein (PRNP). Homozygous mutations with atypical clinical phenotypes have been described but are extremely rare. A Chinese patient presented with a rapidly progressive cognitive and motor disorder in the clinical spectrum of sCJD. Investigations strongly suggested a diagnosis of CJD. He was found to carry a homozygous mutation at PRNP codon 200 (E200D), but there was no known family history of the disorder. The estimated allele frequency of E200D in East Asian populations is incompatible with it being a highly penetrant mutation in the heterozygous state. In our view the homozygous PRNP E200D genotype is likely to be causal of CJD in this patient. Homotypic PrP interactions are well known to favour the development of prion disease. The case is compatible with recessively inherited prion disease.
Sections du résumé
BACKGROUND
BACKGROUND
Inherited prion diseases are rare autosomal dominant disorders associated with diverse clinical presentations. All are associated with mutation of the gene that encodes prion protein (PRNP). Homozygous mutations with atypical clinical phenotypes have been described but are extremely rare.
CASE PRESENTATION
METHODS
A Chinese patient presented with a rapidly progressive cognitive and motor disorder in the clinical spectrum of sCJD. Investigations strongly suggested a diagnosis of CJD. He was found to carry a homozygous mutation at PRNP codon 200 (E200D), but there was no known family history of the disorder. The estimated allele frequency of E200D in East Asian populations is incompatible with it being a highly penetrant mutation in the heterozygous state.
CONCLUSION
CONCLUSIONS
In our view the homozygous PRNP E200D genotype is likely to be causal of CJD in this patient. Homotypic PrP interactions are well known to favour the development of prion disease. The case is compatible with recessively inherited prion disease.
Identifiants
pubmed: 34182938
doi: 10.1186/s12883-021-02274-w
pii: 10.1186/s12883-021-02274-w
pmc: PMC8237416
doi:
Substances chimiques
Prion Proteins
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
248Subventions
Organisme : Medical Research Council
ID : G0400713
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00024/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/J016071/1
Pays : United Kingdom
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