A heterozygous pathogenic variant in the ATP6V1A gene triggering epilepsy in a large Chinese pedigree.

Epilepsy is one of the most common disorders in children, with an incidence rate of approximately 5%. Although an increasing number of genes have been demonstrated to be pathogenic factors in epilepsy, evidence for a potential pathogenic role of ATP6V1A remains limited. Herein, the clinical and genetic data of a 5-year-old boy who experienced seizures at 9 months of age are collected. Genetic variants are screened using whole-exome sequencing (WES), and the effects of the candidate variants are further validated at both the RNA and protein levels. WES reveals a heterozygous variant [NM_001690.4: c .1132 C>T, p.Leu378Phe] of the ATP6V1A gene. This variant is not reported in the public database, but is predicted to be deleterious by multiple software packages, and classified as a variant of unknown significance following the American College of Medical Genetics and Genomics guidelines. Quantitative PCR and western blotting further confirm its down-regulatory role in both the RNA and protein expression of ATP6V1A. This case report confirms the pathogenicity of ATP6V1A in epilepsy with solid experimental evidence, thereby expanding the phenotype spectrum of ATP6V1A variants. More importantly, we show that seizures triggered by ATP6V1A variants could be controlled by Levetiracetam, crucially rescuing the development of the patient.

Relationship between sialorrhea and dysphagia in Chinese patients with Parkinson′s disease / 中华神经科杂志

Objective To explore the prevalence of sialorrhea and its clinical correlation with dysphagia in Chinese patients with Parkinson′s disease ( PD ).Methods One hundred and sixteen consecutive patients with a clinical diagnosis of PD were selected.Demographic data included sex , age, years of education, age at onset of PD, clinical genotype, disease duration, treatment, Hoehn and Yahr (H&Y) stage.Sialorrhea was assessed using the Unified Parkinson′s Disease Rating Scale (UPDRS) Ⅱitem number 6.All patients were studied with videofluoroscopic study of swallowing ( VFSS).Results The prevalence rate of sialorrhea in PD was 59.5% (69/116, 95% CI 50.6%-68.4%).Males were more likely to develop sialorrhea than females (47/70 vs 22/46,χ2 =4.298, P=0.038).PD patients′sialorrhea correlated with oral dysphagia:with food leaking from the mouth ( liquid r=0.229, P=0.014; juice r=0.197, P=0.034;pudding viscosities r=0.231, P=0.013;solid food r=0.255, P=0.006), with more than 1 ml of oral food residues (liquid r=0.319, P<0.01;solid food r=0.185, P=0.047), with delay in food transfer to the root of the tongue (liquid r=0.279, P=0.002; juice r=0.209, P=0.024), and delayed swallow transfer ( pudding viscosities r=0.257, P=0.005).Sialorrhea score was not related to H&Y stage, clinical course and levodopa equivalent doses (LED).The prevalence rate of dysphagia in PD was 87.1%(95% CI 81.0% -93.2%).Liquid was more likely to cause pharyngeal dysphagia ( P=0.03).With the increase in H&Y stage , so did the oral and pharyngeal stages of dysphagia.Late and mid-course was more likely to develop oral and pharyngeal dysphagia than those with early clinical course .Conclusions Sialorrhea and dysphagia are common non-motor symptoms in PD patients.Sialorrhea is more prevalent in males and correlates with oral phase of dysphagia.Liquid is more likely to cause pharyngeal dysphagia.With increase in H&Y stage , so did oral and pharyngeal dysphagia.Even though late clinical course is more likely to develop oral and pharyngeal dysphagia than early clinical course , the comparison between late and intermediate clinical courses does not reach statistical significance .