Format

Send to

Choose Destination
Eur J Hum Genet. 2014 Dec;22(12):1351-6. doi: 10.1038/ejhg.2014.42. Epub 2014 Apr 9.

Predictive testing for inherited prion disease: report of 22 years experience.

Author information

1
NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College Hospitals NHS Trust, London, UK.
2
MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
3
1] NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, University College Hospitals NHS Trust, London, UK [2] MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
4
Clinical Genetics, St Michael's Hospital, Bristol, UK.
5
Clinical Genetics, Great Ormond St Hospital, London, UK.

Abstract

The inherited prion diseases (IPD) are a group of untreatable neurodegenerative diseases that segregate as autosomal dominant traits. Mutations in the prion protein gene (PRNP) were first found to be causal of IPD in 1989, before the molecular genetic characterisation of any other neurodegenerative disease. Predictive testing for IPD has subsequently been carried out at a single UK clinical and research centre for 22 years. We have analysed the uptake, consequences and factors influencing the decision for predictive testing over this period. In all, 104 predictive tests were done on individuals at 50% risk, compared with 135 positive diagnostic tests. Using genealogies from clinical records, we estimated that 23% of those at 50% risk have completed testing. There was no gender bias, and unsurprisingly, there was a slight excess of normal results because some patients were already partly through the risk period because of their age. An unexpectedly large number of patients developed symptoms shortly after predictive testing, suggesting that undisclosed early symptoms of disease may prompt some patients to come forward for predictive testing. Fifteen per cent of predictive tests were done >10 years after molecular diagnosis in a proband. A strong determinant of the timing of testing in these patients was a second diagnosis in the family. IPD may generate infectious prions that might be transmitted by surgical procedures; however, we found no evidence that public health information influenced decisions about predictive testing.

PMID:
24713662
PMCID:
PMC4091984
DOI:
10.1038/ejhg.2014.42
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center