BACKGROUND: Highly penetrant inherited mutations in the prion protein gene (PRNP) offer a window to study the pathobiology of prion disorders. METHOD: Clinical, neuropsychological, and neuroimaging characterization of a kindred. RESULTS: Three of four mutation carriers have progressed to a frontotemporal dementia phenotype. Declines in neuropsychological function coincided with changes in FDG-PET at the identified onset of cognitive impairment. CONCLUSIONS AND RELEVANCE: Gene silencing treatments are on the horizon and when they become available, early detection will be crucial. Longitudinal studies involving familial mutation kindreds can offer important insights into the initial neuropsychological and neuroimaging changes necessary for early detection.
BACKGROUND: Highly penetrant inherited mutations in the prion protein gene (PRNP) offer a window to study the pathobiology of prion disorders. METHOD: Clinical, neuropsychological, and neuroimaging characterization of a kindred. RESULTS: Three of four mutation carriers have progressed to a frontotemporal dementia phenotype. Declines in neuropsychological function coincided with changes in FDG-PET at the identified onset of cognitive impairment. CONCLUSIONS AND RELEVANCE: Gene silencing treatments are on the horizon and when they become available, early detection will be crucial. Longitudinal studies involving familial mutation kindreds can offer important insights into the initial neuropsychological and neuroimaging changes necessary for early detection.
Authors: Neeraj Kumar; Bradley F Boeve; Brendon P Boot; Carolyn F Orr; Joseph Duffy; Bryan K Woodruff; Anil K Nair; Jay Ellison; Karen Kuntz; Kejal Kantarci; Clifford R Jack; Barbara F Westmoreland; Julie A Fields; Matthew Baker; Rosa Rademakers; Joseph E Parisi; Dennis W Dickson Journal: Arch Neurol Date: 2011-09
Authors: Hanna Cho; Jae Yong Choi; Mi Song Hwang; You Jin Kim; Hye Mi Lee; Hye Sun Lee; Jae Hoon Lee; Young Hoon Ryu; Myung Sik Lee; Chul Hyoung Lyoo Journal: Ann Neurol Date: 2016-07-08 Impact factor: 10.422
Authors: Giovanna R Mallucci; Melanie D White; Michael Farmer; Andrew Dickinson; Husna Khatun; Andrew D Powell; Sebastian Brandner; John G R Jefferys; John Collinge Journal: Neuron Date: 2007-02-01 Impact factor: 17.173
Authors: Olga Calero; María J Bullido; Jordi Clarimón; Ana Frank-García; Pablo Martínez-Martín; Alberto Lleó; María Jesús Rey; Alberto Rábano; Rafael Blesa; Teresa Gómez-Isla; Fernando Valdivieso; Jesús de Pedro-Cuesta; Isidro Ferrer; Miguel Calero Journal: PLoS One Date: 2011-07-20 Impact factor: 3.240