Browsing by Author "Momcilovic, Dragana (6603310422)"

Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw-opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia. © 2014 The Authors.

Although coding variants in THAP1 have been causally associated with primary dystonia, the contribution of noncoding variants remains uncertain. Herein, we examine a previously identified Intron 1 variant (c.71+9C>A, rs200209986). Among 1672 subjects with mainly adult-onset primary dystonia, 12 harbored the variant in contrast to 1/1574 controls (P < 0.01). Dystonia classification included cervical dystonia (N = 3), laryngeal dystonia (adductor subtype, N = 3), jaw-opening oromandibular dystonia (N = 1), blepharospasm (N = 2), and unclassified (N = 3). Age of dystonia onset ranged from 25 to 69 years (mean = 54 years). In comparison to controls with no identified THAP1 sequence variants, the c.71+9C>A variant was associated with an elevated ratio of Isoform 1 (NM_018105) to Isoform 2 (NM_199003) in leukocytes. In silico and minigene analyses indicated that c.71+9C>A alters THAP1 splicing. Lymphoblastoid cells harboring the c.71+9C>A variant showed extensive apoptosis with relatively fewer cells in the G2 phase of the cell cycle. Differentially expressed genes from lymphoblastoid cells revealed that the c.71+9C>A variant exerts effects on DNA synthesis, cell growth and proliferation, cell survival, and cytotoxicity. In aggregate, these data indicate that THAP1 c.71+9C>A is a risk factor for adult-onset primary dystonia. © 2014 The Authors.

The basal levels of prolactin (PRL) and their changes after i. v. thyrotropin releasing hormone (TRH) administration after bromocriptine (BCT) pretreatment (BCT/TRH test) were monitored in 12 patients with young‐onset Parkinson's disease (PD) (before 40 years of age) and 10 patients with older‐onset PD (after 40 years of age), as well as in two groups of healthy subjects (10 persons in each), age‐matched with older‐onset (control A) and young‐onset (controlB) parkinsonians. The basal PRL levels were normal in both groups of patients. When given after BCT, TRH induced a significantly lower PRL increase in older‐onset parkinsonians than in controls. This response was even more blunted in young‐onset patients, being significantly more attenuated than in older‐onset PD patients. Copyright © 1993 Movement Disorder Society

The basal levels of prolactin (PRL) and their changes after i. v. thyrotropin releasing hormone (TRH) administration after bromocriptine (BCT) pretreatment (BCT/TRH test) were monitored in 12 patients with young‐onset Parkinson's disease (PD) (before 40 years of age) and 10 patients with older‐onset PD (after 40 years of age), as well as in two groups of healthy subjects (10 persons in each), age‐matched with older‐onset (control A) and young‐onset (controlB) parkinsonians. The basal PRL levels were normal in both groups of patients. When given after BCT, TRH induced a significantly lower PRL increase in older‐onset parkinsonians than in controls. This response was even more blunted in young‐onset patients, being significantly more attenuated than in older‐onset PD patients. Copyright © 1993 Movement Disorder Society