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Childhood Onset in Familial Prion Disease With a Novel Mutation in the PRNP Gene
Ekaterina Rogaeva, PhD;
Cindy Zadikoff, MD;
Jonathan Ponesse, MD;
Gerold Schmitt-Ulms, PhD;
Toshitaka Kawarai, MD;
Christine Sato, BSc;
Shabnam Salehi-Rad, BSc;
Peter St. George-Hyslop, MD, FRCPC;
Anthony E. Lang, MD
Arch Neurol. 2006;63:1016-1021.
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.
Design Detailed neurological examination and sequencing analysis of the MAPT and PRNP genes.
Setting Toronto Western Hospital, Toronto, Ontario.
Patients 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.
Author Affiliations: Centre for Research in Neurodegenerative Diseases (Drs Rogaeva, Schmitt-Ulms, Kawarai, and St. George-Hyslop and Mss Sato and Salehi-Rad) and Division of Neurology (Drs Rogaeva, St. George-Hyslop, and Lang), Department of Medicine, and Toronto Western Hospital Research Institute, Movement Disorders Centre, Toronto Western Hospital (Drs Zadikoff, St. George-Hyslop, and Lang), University of Toronto, and Divisions of Neurology and Developmental Pediatrics, Hospital for Sick Children (Dr Ponesse), Toronto, Ontario.
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