A novel homozygous SYNJ1 mutation in two siblings with typical Parkinson's disease.

BACKGROUND: Mutations in the SYNJ1 have been associated with early onset of atypical Parkinson's disease (PARK20). Patients with PARK20 exhibit a wide phenotypic variability. Here, we report the clinical and genetic findings in two affected siblings with a novel homozygous SYNJ1 mutation. METHODS: A consanguineous family with two affected siblings with Parkinson's disease was recruited. Both siblings underwent detailed neurological examinations. Whole genome sequencing was performed in the proband. RESULTS: Both affected siblings presented with pure parkinsonism with no other atypical symptoms and a slow disease progression. The proband had an excellent response to levodopa. Performing the levodopa challenge test in the proband's older brother resulted in improvements in the parkinsonism signs. Genetic analysis identified a homozygous missense mutation in SYNJ1 (c.2495A > G, p.Y832C) in both of siblings. In silico analyses revealed that the mutation was deleterious. CONCLUSIONS: Screening for SNYJ1 should be considered in patients with typical levodopa-responsive Parkinson's disease.

The correlation of neutrophil-to-lymphocyte ratio with the presence and activity of myasthenia gravis.

Though the pathogenesis of myasthenia gravis (MG) is not fully understood, the role of inflammation has been well appreciated in the development of MG. We aimed to investigate the role of neutrophil-to-lymphocyte ratio (NLR) in MG patients and the relationship between the NLR and the activity of the disease. A total number of 172 MG patients and 207 healthy controls (HC) were enrolled in this study. The MG patients were divided into tertiles according to NLR (low NLR < 1.58, n = 57; intermediate NLR 1.58-2.33, n = 57 and high NLR > 2.33, n = 58). The disease activity assessment was performed according to the standard criteria established by the Myasthenia Gravis Foundation of America. Patients with MG had significantly higher NLR when compared with the HC group (P < 0.0001). The NLR levels were higher in the MG patients with severe disease activity than those with mild disease activity (P < 0.001), meanwhile, median NLR was statistically higher in MG patients with myasthenic crisis (MC) than those without MC (P < 0.001). Incidences of severe disease activity and MC were both higher in the high NLR group, compared to low and intermediate NLR groups (both P < 0.001). Multivariate logistic regression analysis suggested that elevated NLR was an independent predictor of severe disease activity (odds ratio = 13.201, CI% = 1.418-122.938, P = 0.023). These results indicate that NLR may be a simple and useful potential marker in indicating disease activity in patients with MG.

Low serum albumin concentrations are associated with disease severity in patients with myasthenia gravis.

Serum albumin (S-Alb) is a widely used biomarker of nutritional status and disease severity in patients with autoimmune diseases. We investigated the correlation between S-Alb and the severity of myasthenia gravis (MG).A total number of 166 subjects were recruited in the study. Subjects were divided into 3 groups (T1 to T3) by S-Alb levels: T1: 21.1 to 38.4 g/L, T2: 38.5 to 41.5 g/L, T3: 41.6 to 48.9 g/L. Regression analysis was performed to determine the correlation of initial albumin concentrations and the severity of disease of MG.Lower levels of S-Alb were observed in subjects with increased disease severity than those with slight disease severity, meanwhile, incidence of myasthenia crisis increased in the lower albumin tertiles (P < 0.001). The disease severity assessment was performed according to the criteria established by the Myasthenia Gravis Foundation of America. After adjusting for age, sex, body mass index (BMI), and duration of disease, it showed that higher S-Alb concentrations were associated with lower disease severity. Odds ratios (ORs) of T2 to T3 were 0.241 (95% CI: 0.103-0.566, P < 0.001), 0.140 (95% CI: 0.054-0.367, P < 0.001) when compared with subjects in the T1, respectively. When subjects were stratified into hypoalbuminemia and normal albumin groups, we found that the association between S-Alb and MG remained significant in the hypoalbuminemia group only (OR: 0.693, 95% CI: 0.550-0.874, P = 0.002) after further adjustment for age, sex, BMI, and duration of disease.This is the first study to demonstrate that S-Alb was independently associated with MG severity. In patients with low S-Alb, S-Alb concentration could be a potential biomarker for MG disability.