TY - JOUR
T1 - Progranulin mutations in primary progressive aphasia
T2 - The PPA1 and PPA3 families
AU - Mesulam, Marsel
AU - Johnson, Nancy
AU - Krefft, Thomas A.
AU - Gass, Jennifer M.
AU - Cannon, Ashley D.
AU - Adamson, Jennifer L.
AU - Bigio, Eileen H.
AU - Weintraub, Sandra
AU - Dickson, Dennis W.
AU - Hutton, Michael L.
AU - Graff-Radford, Neill R.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/1
Y1 - 2007/1
N2 - Background: Primary progressive aphasia (PPA) is a language-based dementia characterized by fluent or nonfluent language disorder as its principal feature. Objective: To describe progranulin gene mutations in 2 families with PPA. Design: Report of affected families. Setting: Academic research. Patients: Two families, PPA1 and PPA3, were studied. Genomic DNA was isolated from 3 of 4 siblings in PPA1, from all 3 siblings in PPA3, and from more than 200 control subjects. Main Outcome Measures: All 12 coding exons of the progranulin gene and the 5′ and 3′ untranslated regions were amplified by polymerase chain reaction and were sequenced in both directions using relevant primers. Results: Both affected members of PPA1 for whom DNA was available and both affected sisters of PPA3 had a progranulin gene mutation not found in the unaffected siblings or in the controls. The mutations likely cause a null allele and a reduction in the level of functional progranulin protein. Both affected members of PPA1 with autopsies had frontotemporal lobar degeneration with taunegative ubiquinated inclusions. Conclusions: To our knowledge, these are the only known families in which affected members display phenotypical homogeneity for PPA in the initial stages of the disease. In both families, the disease segregated with progranulin gene mutations. Whether progranulin dysfunction also extends to sporadic PPA and how it affects the initial anatomical specificity of neurodegeneration remain to be determined.
AB - Background: Primary progressive aphasia (PPA) is a language-based dementia characterized by fluent or nonfluent language disorder as its principal feature. Objective: To describe progranulin gene mutations in 2 families with PPA. Design: Report of affected families. Setting: Academic research. Patients: Two families, PPA1 and PPA3, were studied. Genomic DNA was isolated from 3 of 4 siblings in PPA1, from all 3 siblings in PPA3, and from more than 200 control subjects. Main Outcome Measures: All 12 coding exons of the progranulin gene and the 5′ and 3′ untranslated regions were amplified by polymerase chain reaction and were sequenced in both directions using relevant primers. Results: Both affected members of PPA1 for whom DNA was available and both affected sisters of PPA3 had a progranulin gene mutation not found in the unaffected siblings or in the controls. The mutations likely cause a null allele and a reduction in the level of functional progranulin protein. Both affected members of PPA1 with autopsies had frontotemporal lobar degeneration with taunegative ubiquinated inclusions. Conclusions: To our knowledge, these are the only known families in which affected members display phenotypical homogeneity for PPA in the initial stages of the disease. In both families, the disease segregated with progranulin gene mutations. Whether progranulin dysfunction also extends to sporadic PPA and how it affects the initial anatomical specificity of neurodegeneration remain to be determined.
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U2 - 10.1001/archneur.64.1.43
DO - 10.1001/archneur.64.1.43
M3 - Article
C2 - 17210807
AN - SCOPUS:33846094364
SN - 0003-9942
VL - 64
SP - 43
EP - 47
JO - Archives of neurology
JF - Archives of neurology
IS - 1
ER -