Hülya Apaydın1, Sibel Özekmekçi1, Derya Uludüz1, Yasuko Hatano2, Yoshikuni Mizuno2, Nobutaka Hattori2

1Department Of Neurology, İstanbul University, Cerrahpasa Faculty Of Medicine, Turkey
2Neurology Clinic, University Of Juntendo, Faculty Of Medicine, Tokyo, Japan

Keywords: PARK7, DJ-1 gene, early-onset, autosomal recessive parkinsonism, dystonia, motor complications, psychosis, impulse control disorder


OBJECTIVE: Genetic studies for Parkinson’s disease (PD) which have been increased during last few years have shown that parkin (PARK2), DJ-1 (PARK7) and PINK-1 (PARK6) mutations can cause autosomal recessive early-onset parkinsonism.

OBJECTIVE: The aim of this study was to investigate by genetic screening methods, the presence of possible genetic mutations in two siblings who have developed PD.

METHODS: In these two brothers, PD started at the age of 48 with cervical dystonia and bradykinesia on the left arm, and 56 with tremor on the right hand, respectively. Although they had a favorable response to levodopa, they developed wearing-off phenomenon without dyskinesia on the 4th year. Besides dystonia, the younger brother experienced psychosis and impulse control disorder, as well. Family history revealed first degree consanguinity and the father had also a diagnosis of PD. PD progressed rather slowly in both, but unfortunately the older brother died due to lung cancer 10 years after the initial diagnosis of PD, while he was on the stage 2 of Hoehn-Yahr scale. The younger brother is still on our follow-up at the 7th year of his PD. Informed consent was obtained and blood samples were sent to the genetic department of Juntendo University in Japan for genetic analysis. Parkin gene mutation and DJ-1 gene mutation were analyzed on the PARK7 locus, by automated direct nucleotide sequencing and performed gene dosage assay using TaqMan real-time quantitive PCR.

RESULTS: After excluding the parkin mutation the presence of PARK7 was detected in both siblings with haplotype analysis. DJ-1 gene mutation analysis responsible for PARK7, revealed a deletion on intron 1.

CONCLUSION: A rarely encountered PARK7 mutation was identified in two brothers having slowly progressive PD and a favorable response to levodopa, one of whom also had psychotic symptoms. As in the presented cases, the genetic studies performed on early-onset PD patients with positive family history provide significant contributions to the sub-group identification of the disease which exhibits clinical heterogeneity.