Mutations in the LRRK2 gene are a cause of autosomal dominant Parkinson's disease (PD). Whether LRRK2 variants influence susceptibility to the commoner, sporadic forms of PD remains largely unknown. Data are particularly limited concerning the Asian population. In search for novel, biologically relevant variants, we sequenced the LRRK2 coding region in Taiwanese patients with PD. Four newly identified variants and another variant recently found in a Taiwanese PD family were tested for association with the disease in a sample of 608 PD cases and 373 ethnically matched controls. Heterozygosity for the Gly2385Arg variant was significantly more frequent among PD patients than controls (nominal p value=0.004, corrected for multiple comparisons=0.012, gender- and age-adjusted odds ratio=2.24, 95% C.I.: 1.29-3.88); this variant was uniformly distributed across genders and age strata. Two novel variants, Met1869Val and Glu1874Stop, were found in one PD case each; their pathogenic role remains, therefore, uncertain. The remaining two novel variants (Ala419Val and Pro755Leu) were present with similar frequency in cases and controls, and were therefore, interpreted as disease-unrelated polymorphisms. Our findings suggest that the LRRK2 Gly2385Arg is the first identified, functionally relevant variant, which acts as common risk factor for sporadic PD in the population of Chinese ethnicity.

The phenotype associated with ECHS1 mutations might be milder than reported earlier, compatible with prolonged survival, and also includes isolated paroxysmal exercise-induced dystonia. ECHS1 screening should be considered in patients with otherwise unexplained paroxysmal exercise-induced dystonia, in addition to those with Leigh and Leigh-like syndromes. Diet regimens and detoxifying agents represent potential therapeutic strategies. © 2016 International Parkinson and Movement Disorder Society.

Mutations of PLA2G6 gene have been lately proposed to be the causative gene for PARK14 in patients with autosomal recessive young-onset parkinsonism (YOPD). The role of PLA2G6 mutations as a risk factor for Parkinson's disease is not clear. To study the PLA2G6 mutations in PARK14-linked patients and its association with the onset of sporadic Parkinson's disease (sPD), sequencing and gene dosage analyses were carried out in 25 patients (onset age ≦30 years) then the identified variants were assessed in 956 sporadic PD (sPD) patients and 802 age-matched healthy controls. Four genetic variants were identified; one patient had homozygous c.991G > T (p.Asp331Tyr) mutation, two had compound heterozygous c.991G > T/c.1077G > A (p.Met358IlefsX) mutation, one had single c.1976A > G (p.Asn659Ser) mutation, and one patient had an exon 1 hetero-deletion. The c.1077G > A mutation resulted in a 4-bp deletion in leukocyte mRNA by activating a cryptic splice site in exon 7. Only p.Asp331Tyr was identified in four sPD patients and four controls. The onset age for PLA2G6 mutation carriers was younger than that for sPD (29.86 ± 8.59 vs. 56.84 ± 11.33 years, P = 0.0002). The analysis of previously reported PARK14 patients revealed that those who carried a truncated mutation tended to have a complicated phenotype and atrophies of cortex and cerebellum. In conclusion, PLA2G6 mutation was the second common genetic cause after PRKN mutation in our YOPD patients and might be a risk factor for early-onset PD in Han Chinese. Additionally, mutation data should be interpreted carefully because even a synonymous mutation could cause abnormal mRNA splicing.