Aims: CHD4 gene, encoding chromodomain helicase DNA-binding protein 4, is a vital gene for fetal development. In this study, we aimed to explore the association between CHD4 variants and idiopathic epilepsy. Methods: Trios-based whole-exome sequencing was performed in a cohort of 482 patients with childhood idiopathic epilepsy. The Clinical Validity Framework of ClinGen and an evaluating method from five clinical-genetic aspects were used to determine the association between CHD4 variants and epilepsy. Results: Four novel heterozygous missense mutations in CHD4, including two de novo mutations (c.1597A>G/p.K533E and c.4936G>A/p.E1646K) and two inherited mutations with co-segregation (c.856C>G/p.P286A and c.4977C>G/p.D1659E), were identified in four unrelated families with eight individuals affected. Seven affected individuals had sinus arrhythmia. From the molecular sub-regional point of view, the missense mutations located in the central regions from SNF2-like region to DUF1087 domain were associated with multisystem developmental disorders, while idiopathic epilepsy-related mutations were outside this region. Strong evidence from ClinGen Clinical Validity Framework and evidences from four of the five clinical-genetic aspects suggested an association between CHD4 variants and epilepsy.Conclusions: CHD4 was potentially a candidate pathogenic gene of childhood idiopathic epilepsy with arrhythmia. The molecular sub-regional effect of CHD4 mutations helped explaining the mechanisms underlying phenotypic variations.

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Background: Efficient assessment of patients after ischemic stroke has important reference value for doctors to choose appropriate treatment and rehabilitation method for patients. Our study aimed to develop a new prognostic model for predicting outcomes three months after ischemic stroke among Chinese Population． Methods: A prospective observational cohort study among ischemic stroke patients presenting to Emergency Department in the Second Affiliated Hospital of Guangzhou Medical University was conducted from May 2012 to June 2013. Demographic data of ischemic stroke patients, assessment of NIHSS and laboratory results were collected. Based on three-month modified Rankin Scale (mRS) ischemic stroke patients were divided into either favorable outcome (mRS: 0-2) or unfavorable outcome groups (mRS: 3-6). The variables closely associated with prognosis of ischemic stroke were selected to develop the new prognostic model consisted of four parameters: NIHSS, age, atrial fibrillation (AF), prealbumin (PA). The prognostic value of the modified prognostic model (NAAP: NIHSS+Age+AF+PA) was then compared with NIHSS alone.Results: A total of 454 patients with suspected stroke were recruited. 186 patients with ischemic stroke were included in the final analysis. There were 105 (56.5%) cases of ischemic stroke with favorable outcome, and 81 (43.5%) cases of ischemic stroke with unfavorable outcome. A new prognostic model, NAAP was developed.The area under curve (AUC) of NAAP was 0.861 (95%CI: 0.803-0.907), whilst the AUC of NIHSS was 0.783 (95%CI: 0.717-0.840), (P=0.0048). Decision curve analysis (DCA) showed that NAAP had a higher net benefit for threshold probabilities of 65% for predictive risk of poor outcomes. Conclusion:The modified prognostic model, NAAP may be a better prognostic tool for predicting 3-month unfavorable outcomes for ischemic stroke than NIHSS alone.

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