Overall progress and preliminary data: The research subjects for collection of clinical material, skin biopsies for fibroblast cultures, and the blood specimens for the genetic analysis were recruited through the Clinical Core B, subcontract to the Columbia University (Columbia), Pi's: K. Marder, MD, MPH and S. Przedborski, MD, PhD, through the Project 1, subcontract to the Mayo Clinic Florida (MCF), Pi's: Z. Wszoiek, MD and M. Farrer, PhD, and through the Project 2, subcontract to the Johns Hopkins Hospital (JHH), PI: T. Dawson, MD, PhD. The IRB Committees of all participating Institutions approved consent forms with special language requested by Coriell Institute (Coriell) allowing sharing of the material with Coriell and members of this Consortium. Core B planned to recruit 30 Parkinson disease (PD) cases, 24 with known gene mutations {PRKN. LRRK2 G2019S and GBA N370S and L444P), and 6 PD cases without known gene mutations. Project 1 planned to recruit 15 PD/Parkinsonism patients, all with a known genetic cause including SNCA (A53T and multiplication), LRRK2 (G2019S, I2020T, R1441C, Y1699C, and G2385R), PRKN and PINK1 (mutation status to be determined in the future), /W>AP7 (N279K, P301L, and P301S), PGRN (C268A), and DCTN1 (G71R and G59S) gene mutations. No plans for recruitment of research subjects were proposed under the Project 2 Collected clinical material: We have exceeded our plans by recruiting 83 PD patients, controls and patients with atypical parkinsonism and movement disorders (Table 2). Columbia recruited 29 GO PD cases with mutations. An ad(iiitional 5 spouse controls and 12 age and sex matched PD cases who do not carry known mutations were recruited through the Columbia Udall Center and are age/gender matched to the majority of cases using the exact same protocol including the PD DOC battery. MCF was able to recruit 26 patients, carriers of genes that we have not foreseen to be available at the time of grant preparation such as for example carriers of TDP-43, S0D1 or FUS gene mutations. JHH was able to recruit 10 patients. It should also be noted that when possible we recruited research subjects with rare forms of atypical Parkinsonism, ALS and HD to support the two other Consortia (bottom of Table 2). The HD case enrolled at Columbia completed a 3 generation family for the HD IPS consortium. Interestingly, the MCF ALS patient who carried a FUS gene mutation had lower motor muscle weakness and chorea. This patient recently died and at autopsy showed fus inclusions in motor neurons, substantia nigra and basal ganglia nuclei highlighting the importance of collecting such rarer cases when opportunity presents, since the specimen obtained from this particular patient may be of significant importance to all three NINDS Consortia. Other research subjects who provided skin biopsies are also enrolled in Columbia and MCF autopsy programs. All mutation carriers, controls, and sporadic PD cases had their genotypes confirmed by Dr. L. Clark (Columbia) or Dr. O. Ross (MCF).
