Related Experiment Video

Updated: Jul 5, 2026

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
09:34

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Published on: April 4, 2018

Evidence for a pathogenic role of different mutations at codon 188 of PRNP

Sigrun Roeber1, Eva-Maria Grasbon-Frodl, Otto Windl

  • 1Center for Neuropathology and Prion Research, Ludwig-Maximilians-University, München, Germany.

Plos One
|May 15, 2008
PubMed

Insights

Two novel prion protein gene (PRNP) mutations, T188R and T188K, were identified in patients with Creutzfeldt-Jakob disease (CJD). The T188K mutation is likely pathogenic, causing genetic CJD with reduced penetrance.

Area of Science:

  • Neurogenetics
  • Molecular Biology
  • Prion Diseases

Background:

  • Familial Creutzfeldt-Jakob disease (CJD) shares clinical and pathological features with sporadic CJD.
  • Identifying novel mutations in the prion protein gene (PRNP) is crucial for diagnosing genetic CJD.
  • PRNP mutations are key determinants of inherited prion disorders.

Purpose of the Study:

  • To investigate rare PRNP mutations at codon 188 in patients with CJD-like symptoms.
  • To determine the pathogenicity and prevalence of T188R and T188K mutations.
  • To differentiate genetic CJD from sporadic CJD based on PRNP mutations.

Main Methods:

  • Genetic sequencing of the PRNP gene in affected patients and control populations.
  • Clinical and pathological evaluation of patients with identified mutations.
  • Prevalence studies in sporadic CJD cases and healthy individuals.

Main Results:

  • Two distinct PRNP mutations, T188R and T188K, were identified in four patients with CJD-like illness.
  • Neither mutation was found in 593 sporadic CJD cases or 735 healthy controls.
  • The T188K mutation was observed in three patients and a father with reduced penetrance, suggesting pathogenicity.

Conclusions:

  • The T188K mutation is strongly implicated as a cause of genetic CJD.
  • The T188K mutation exhibits incomplete penetrance, with affected individuals showing variable disease onset.
  • Further research is needed to confirm the pathogenicity of the T188R mutation.

Related Concept Videos

Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Mutations01:39

Mutations

Overview
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...