| Geno
|
Mag
|
Summary
|
| (A;G)
|
6.5
|
PrP D178N pathogenic mutation - leads to CJD or FFI
|
| (G;G)
|
0
|
PrP codon 178 (D) - non pathogenic variant
|
aka c.532G>A (p.Asp178Asn or D178N)
This SNP codes for residue 178 of the Prion protein gene. Normally Aspartate, a polymorphism can create the D178N mutation which is linked to inherited Creutzfeldt-Jakob disease or Fatal Familial Insomnia. A number of factors influence this, including PrP codon 129, Rs1799990, with 129MM homozygotes being more likely to develop Fatal Familial Insomnia.
2016 Nature essay about this mutation, discussing use of ExAC to estimate penetrance (which at least for this mutation, D178N, turns out to be high): http://www.nature.com/news/a-radical-revision-of-human-genetics-1.20779
A 2019 Wired magazine article chronicles the efforts of one couple to find a cure for FFI, including the mention of upcoming clinical trials for carriers of the D178N mutation.
References[edit]
[PMID 12420099] Mutations of the prion protein gene phenotypic spectrum.
[PMID 1671440] The initial discovery of the D178N mutation in a Finnish family
[PMID 1353341] Linkage analysis of 7 families indicated strong likelihood of developing Creuzfeldt-Jakob disease given the D178N mutation, with a LOD score of 5.30.
[PMID 16227536
] Clinical, pathological, and genetic data were determined for a number of D178N patients, showing that symptoms lay on a spectrum from typical Creutzfeldt-Jakob disease to Fatal Familial Insomnia.
] Clinical, pathological, and genetic data were determined for a number of D178N patients, showing that symptoms lay on a spectrum from typical Creutzfeldt-Jakob disease to Fatal Familial Insomnia.
