Childhood onset in familial prion disease with a novel mutation in the PRNP gene.
BACKGROUND
Up to 15% of cases of prion diseases are due to the autosomal dominant inheritance of coding PRNP mutations.


OBJECTIVE
To describe the unique clinical and genetic findings in a family of East Indian origin with autosomal dominant inheritance of a novel PRNP mutation.


METHODS
Detailed neurological examination and sequencing analysis of the MAPT and PRNP genes.


METHODS
Toronto Western Hospital, Toronto, Ontario.


METHODS
Five available members of a family of East Indian origin with a rapidly progressive neurodegenerative disorder characterized by dementia, motor decline, and ataxia.


RESULTS
We identified a novel Pro105Thr mutation in the PRNP gene in all of the 3 clinically affected family members but not in their unaffected relatives or normal controls. Although 5 of 6 affected family members had a relatively homogeneous phenotype and age at onset (range, 33-41 years), 1 of the 6 patients developed the disease at age 13 years.


CONCLUSIONS
A novel mutation in the PRNP gene was identified in all of the available, clinically affected members of this family with a rapidly progressive neurodegenerative disease. To our knowledge, the propositus represents the youngest individual with inherited prion disease described to date.
Rogaeva
Ekaterina
E
Centre for Research in Neurodegenerative Diseases, Department of Medicine, Toronto, Ontario, Canada.
Zadikoff
Cindy
C
Ponesse
Jonathan
J
Schmitt-Ulms
Gerold
G
Kawarai
Toshitaka
T
Sato
Christine
C
Salehi-Rad
Shabnam
S
St George-Hyslop
Peter
P
Lang
Anthony E
AE
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000682:Amyloid / Q000235:genetics*; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017096:Prion Diseases / Q000235:genetics*; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors / Q000235:genetics*
D000682:Amyloid; C512656:PRNP protein, human; D000072002:Prion Proteins; D011328:Prions; D011498:Protein Precursors