TY - JOUR
T1 - Three families with Perry syndrome from distinct parts of the world
AU - Tacik, Pawel
AU - Fiesel, Fabienne C.
AU - Fujioka, Shinsuke
AU - Ross, Owen A.
AU - Pretelt, Felipe
AU - Castañeda Cardona, Camilo
AU - Kidd, Alexa
AU - Hlavac, Michael
AU - Raizis, Anthony
AU - Okun, Michael S.
AU - Traynor, Sharleen
AU - Strongosky, Audrey J.
AU - Springer, Wolfdieter
AU - Wszolek, Zbigniew K.
N1 - Funding Information:
Pawel Tacik is supported by the Max Kade Foundation.
Funding Information:
Michael S. Okun serves as a consultant for the National Parkinson Foundation, and has received research grants from NIH, NPF, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Dr. Okun has previously received honoraria, but in the past >36 months has received no support from industry. Dr. Okun has received royalties for publications with Demos, Manson, Amazon, and Cambridge (movement disorders books). Dr. Okun is an associate editor for New England Journal of Medicine, Journal Watch Neurology. Dr. Okun has participated in CME activities on movement disorders in the last 36 months sponsored by PeerView, Prime, and by Vanderbilt University. The institution and not Dr. Okun receives grants from Medtronic and ANS/St. Jude, and the PI has no financial interest in these grants. Dr. Okun has participated as a site PI and/or co-I for several NIH, foundation, and industry sponsored trials over the years but has not received honoraria.
Funding Information:
Zbigniew K. Wszolek is partially supported by the NIH/NINDS P50 NS072187, the Michael J. Fox Foundation for Parkinson's Research, and the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch.
Funding Information:
Shinsuke Fujioka is partially supported by the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch.
Funding Information:
Owen A. Ross is partially supported by NIH/NINDS R01 NS078086 and supported by the NIH/NINDS P50 NS072187.
Funding Information:
Wolfdieter Springer is partially supported by the Mayo Clinic Center for Individualized Medicine, the Marriott Family Foundation and the Gerstner Family Career Development Award.
PY - 2014/8
Y1 - 2014/8
N2 - Perry syndrome consists of autosomal dominant Parkinsonism, depression, weight loss, and central hypoventilation. Eight mutations in 16 families have been reported: p.F52L, p.G67D, p.G71R, p.G71E, p.G71A, p.T72P, p.Q74P, and p.Y78C located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome 2p13.1. Methods: Genealogical, clinical, genetic, and functional studies were performed in three kindreds from New Zealand, the United States, and Colombia. A diaphragmatic pacemaker was implanted in the proband from the Colombian family to treat her respiratory insufficiency. Dopaminergic therapy was initiated in probands from two families. Results: Besides the probands, 17 symptomatic relatives from all families were identified. The cardinal signs of Perry syndrome were present in all three probands with symptomatic disease onset in their fifth or sixth decade of life. Parkinsonism was moderate with a partial response to dopaminergic treatment. All affected persons but two died of respiratory insufficiency. The proband from the Colombian family is alive most likely due to early diagnosis and implantation of a diaphragmatic pacemaker. Two-and-a-half-year follow-up examination has revealed that the diaphragmatic pacemaker is optimally functioning without any major complications. In the Colombian and US families, the DCTN1 p.G71R and in the New Zealand family the DCTN1 p.Y78C mutations were identified. In functional assays, both mutations altered microtubule binding consistent with a pathogenic role. Conclusions: Perry syndrome is a rare condition, but new cases are expected to be diagnosed worldwide. Early diagnosis prevents life-threatening acute respiratory failure. Diaphragmatic pacemakers should be considered as an effective symptomatic treatment option.
AB - Perry syndrome consists of autosomal dominant Parkinsonism, depression, weight loss, and central hypoventilation. Eight mutations in 16 families have been reported: p.F52L, p.G67D, p.G71R, p.G71E, p.G71A, p.T72P, p.Q74P, and p.Y78C located in exon 2 of the dynactin 1 (DCTN1) gene on chromosome 2p13.1. Methods: Genealogical, clinical, genetic, and functional studies were performed in three kindreds from New Zealand, the United States, and Colombia. A diaphragmatic pacemaker was implanted in the proband from the Colombian family to treat her respiratory insufficiency. Dopaminergic therapy was initiated in probands from two families. Results: Besides the probands, 17 symptomatic relatives from all families were identified. The cardinal signs of Perry syndrome were present in all three probands with symptomatic disease onset in their fifth or sixth decade of life. Parkinsonism was moderate with a partial response to dopaminergic treatment. All affected persons but two died of respiratory insufficiency. The proband from the Colombian family is alive most likely due to early diagnosis and implantation of a diaphragmatic pacemaker. Two-and-a-half-year follow-up examination has revealed that the diaphragmatic pacemaker is optimally functioning without any major complications. In the Colombian and US families, the DCTN1 p.G71R and in the New Zealand family the DCTN1 p.Y78C mutations were identified. In functional assays, both mutations altered microtubule binding consistent with a pathogenic role. Conclusions: Perry syndrome is a rare condition, but new cases are expected to be diagnosed worldwide. Early diagnosis prevents life-threatening acute respiratory failure. Diaphragmatic pacemakers should be considered as an effective symptomatic treatment option.
KW - DCTN1
KW - Familial
KW - Gene mutation
KW - Parkinsonism
KW - Perry syndrome
KW - Respiratory insufficiency
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U2 - 10.1016/j.parkreldis.2014.05.004
DO - 10.1016/j.parkreldis.2014.05.004
M3 - Article
C2 - 24881494
AN - SCOPUS:84905251154
SN - 1353-8020
VL - 20
SP - 884
EP - 888
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 8
ER -