TY - JOUR
T1 - Similar clinical and neuroimaging features in monozygotic twin pair with mutation in progranulin
AU - McDade, E.
AU - Boeve, B. F.
AU - Burrus, T. M.
AU - Boot, B. P.
AU - Kantarci, K.
AU - Fields, J.
AU - Lowe, V. J.
AU - Peller, P.
AU - Knopman, D.
AU - Baker, M.
AU - Finch, N.
AU - Rademakers, R.
AU - Petersen, R.
N1 - Funding Information:
Study funding: Supported by grants P50-AG016574 and R01-AG011378 and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer's Disease Research Program of the Mayo Foundation.
Funding Information:
Dr. McDade reports no disclosures. Dr. Boeve receives publishing royalties for Behavioral Neurology of Dementia (Cambridge Medicine, 2009) and receives research support from Cephalon, Inc., Allon Pharmaceuticals, the NIH (NIA, CIDR), and the Mangurian Foundation. Dr. Burrus and Dr. Boot report no disclosures. Dr. Kantarci receives research support from the NIH. Dr. Fields serves on the editorial advisory board of International Journal of Neuroscience and has received NIH funding through the Building Interdisciplinary Research Careers in Women's Health program. Dr. Lowe serves on a scientific advisory board for Bayer Schering Pharma and receives/has received research support from GE Healthcare, Siemens Molecular Imaging, Avid Radiopharmaceuticals, Inc., the NIH/NIA, the MN Partnership for Biotechnology and Medical Genomics, and The Leukemia & Lymphoma Society. Dr. Peller has received research support from GE Healthcare. Dr. Knopman serves as Deputy Editor for Neurology®; serves on a data safety monitoring board for Eli Lilly and Company; has served as a consultant for Elan/Janssen AI; is an investigator in clinical trials sponsored by Elan/Janssen AI, Baxter International Inc. and Forest Laboratories, Inc.; and receives research support from the NIH. M. Baker holds patents re: Methods and materials for detecting and treating dementia. N. Finch reports no disclosures. Dr. Rademakers holds patents re: Methods and materials for detecting and treating dementia and receives research support from the NIH, the Pacific Alzheimer Research Foundation (Canada), the Association for Frontotemporal Dementia, the Amyotrophic Lateral Sclerosis Association, CurePSP, and the Consortium for Frontotemporal Dementia. Dr. Petersen serves on scientific advisory boards for Pfizer Inc, the Alzheimer's Association, the National Advisory Council on Aging (NIA), Elan/Janssen AI, and GE Healthcare; receives royalties from publishing Mild Cognitive Impairment (Oxford University Press, 2003); serves as a consultant for Elan/Janssen AI and GE Healthcare; and receives research support from the NIH/NIA.
PY - 2012/4/17
Y1 - 2012/4/17
N2 - Objective: To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN). Methods: We studied a twin pair with an exon 4 gene deletion in the PGRN gene. Both twins had clinical and neuropsychological examinations as well as structural MRI and fluorodeoxyglucose PET (FDG-PET) scans. PGRN gene sequencing was performed followed by progranulin ELISA in plasma. Results: Both twins manifested symptoms within 3 years of each other, with early behavioral, language, dysexecutive, and memory problems. MRI and FDG-PET imaging demonstrated a strikingly similar topography of findings with clear left hemisphere predominance. Serum progranulin levels in both were well below those from a normal population sample. Conclusions: Compared with the heterogeneity seen in many families with PGRN mutations, these monozygotic twins demonstrated strong clinical, neuroimaging, and serum progranulin level similarities, demonstrating the importance of shared genetic profiles beyond environmental influences in the symptomatic expression of the disease.
AB - Objective: To report the phenotypic characterization of monozygotic twins with mutations encoding progranulin (PGRN). Methods: We studied a twin pair with an exon 4 gene deletion in the PGRN gene. Both twins had clinical and neuropsychological examinations as well as structural MRI and fluorodeoxyglucose PET (FDG-PET) scans. PGRN gene sequencing was performed followed by progranulin ELISA in plasma. Results: Both twins manifested symptoms within 3 years of each other, with early behavioral, language, dysexecutive, and memory problems. MRI and FDG-PET imaging demonstrated a strikingly similar topography of findings with clear left hemisphere predominance. Serum progranulin levels in both were well below those from a normal population sample. Conclusions: Compared with the heterogeneity seen in many families with PGRN mutations, these monozygotic twins demonstrated strong clinical, neuroimaging, and serum progranulin level similarities, demonstrating the importance of shared genetic profiles beyond environmental influences in the symptomatic expression of the disease.
UR - http://www.scopus.com/inward/record.url?scp=84860719745&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318251594c
DO - 10.1212/WNL.0b013e318251594c
M3 - Article
C2 - 22491866
AN - SCOPUS:84860719745
VL - 78
SP - 1245
EP - 1249
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 16
ER -