Abstract|Movement Disorders 3| Volume 357, SUPPLEMENT 1, e58-e59, October 15, 2015

Clinicogenetic study of CHCHD2 in patients with autosomal dominant familial Parkinson's disease

      We have identified a novel causative gene, CHCHD2 responsible for patients with autosomal dominant cases of Parkinson's disease (PD). Family members had a missense mutation (CHCHD2, 182C>T, Thr61Ile) in family A by next-generation sequencing. We obtained samples from a further 340 index patients with autosomal dominant PD, 517 patients with sporadic PD, and 559 controls. Additional three CHCHD2 mutations in four of 341 index cases from independent families with autosomal dominant PD were detected by CHCHD2 mutation screening: 182C>T (Thr61Ile), 434G>A (Arg145Gln), and 300 + 5G>A. In SH-SY5Y cells, the 300+5G>A mutation but not the other two mutations caused exon 2 skipping. CHCHD2 mutations could be a cause for autosomal dominant PD. Clinical phenotypes of patients with CHCHD2 mutations show tremor dominant PD and uptake of 123I-MIBG myocardial scintigraphy of one patient from family A is decreasing. However, dementia and urinary urgency were not observed among all patients with CHCHD2 mutations so far. Clinical phenotypes are very similar to those of PARK8 except for dementia. Taken together, clinical phenotypes are benign including good responsiveness to levodopa compared to PARK8. Further studies will be needed to evaluate the clinical symptoms such as the presence of depression or olfactory dysfunctions.