TY - JOUR
T1 - DCTN1-related neurodegeneration
T2 - Perry syndrome and beyond
AU - Konno, Takuya
AU - Ross, Owen A.
AU - Teive, Hélio A.G.
AU - Sławek, Jarosław
AU - Dickson, Dennis W.
AU - Wszolek, Zbigniew K.
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/8
Y1 - 2017/8
N2 - Perry syndrome (PS) is a rare hereditary neurodegenerative disease characterized by autosomal dominant parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and distinct TDP-43 pathology. The mutated causative gene for PS is DCTN1, which encodes the dynactin subunit p150Glued. Dynactin is a motor protein involved in axonal transport; the p150Glued subunit has a critical role in the overall function. Since the discovery of DCTN1 in PS, it has been increasingly recognized that DCTN1 mutations can exhibit more diverse phenotypes than previously thought. Progressive supranuclear palsy- and/or frontotemporal dementia-like phenotypes have been associated with the PS phenotypes. In addition, DCTN1 mutations were identified in a family with motor-neuron disease before the discovery in PS. In this review, we analyze the clinical and genetic aspects of DCTN1-related neurodegeneration and discuss its pathogenesis. We also describe three families with PS, Canadian, Polish, and Brazilian. DCTN1 mutation was newly identified in two of them, the Canadian and Polish families. The Canadian family was first described in late 1970's but was never genetically tested. We recently had the opportunity to evaluate this family and to test the gene status of an affected family member. The Polish family is newly identified and is the first PS family in Poland. Although still rare, DCTN1-related neurodegeneration needs to be considered in a differential diagnosis of parkinsonian disorders, frontotemporal dementia, and motor-neuron diseases, especially if there is family history.
AB - Perry syndrome (PS) is a rare hereditary neurodegenerative disease characterized by autosomal dominant parkinsonism, psychiatric symptoms, weight loss, central hypoventilation, and distinct TDP-43 pathology. The mutated causative gene for PS is DCTN1, which encodes the dynactin subunit p150Glued. Dynactin is a motor protein involved in axonal transport; the p150Glued subunit has a critical role in the overall function. Since the discovery of DCTN1 in PS, it has been increasingly recognized that DCTN1 mutations can exhibit more diverse phenotypes than previously thought. Progressive supranuclear palsy- and/or frontotemporal dementia-like phenotypes have been associated with the PS phenotypes. In addition, DCTN1 mutations were identified in a family with motor-neuron disease before the discovery in PS. In this review, we analyze the clinical and genetic aspects of DCTN1-related neurodegeneration and discuss its pathogenesis. We also describe three families with PS, Canadian, Polish, and Brazilian. DCTN1 mutation was newly identified in two of them, the Canadian and Polish families. The Canadian family was first described in late 1970's but was never genetically tested. We recently had the opportunity to evaluate this family and to test the gene status of an affected family member. The Polish family is newly identified and is the first PS family in Poland. Although still rare, DCTN1-related neurodegeneration needs to be considered in a differential diagnosis of parkinsonian disorders, frontotemporal dementia, and motor-neuron diseases, especially if there is family history.
KW - Atypical parkinsonism
KW - DCTN1
KW - Dynactin
KW - FTD
KW - Genetics
KW - PSP
KW - Perry syndrome
KW - Review
KW - TDP-43
UR - http://www.scopus.com/inward/record.url?scp=85020721807&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85020721807&partnerID=8YFLogxK
U2 - 10.1016/j.parkreldis.2017.06.004
DO - 10.1016/j.parkreldis.2017.06.004
M3 - Review article
C2 - 28625595
AN - SCOPUS:85020721807
SN - 1353-8020
VL - 41
SP - 14
EP - 24
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
ER -