ABSTRACT
Early-onset epilepsy is a neurological abnormality in childhood, and it is especially common in the first 2 years after birth. Seizures in early life mostly result from structural or metabolic disorders in the brain, and the genetic causes of idiopathic seizures have been extensively investigated. In this study, we identified four missense mutations in the SETD1A gene (SET domain-containing 1A, histone lysine methyltransferase): three de novo mutations in three individuals and one inherited mutation in a four-generation family. Whole-exome sequencing indicated that all four of these mutations were responsible for the seizures. Mutations of SETD1A have been implicated in schizophrenia and developmental disorders, so we examined the role of the four mutations (R913C, Q269R, G1369R, and R1392H) in neural development. We found that their expression in mouse primary cortical neurons affected excitatory synapse development. Moreover, expression of the R913C mutation also affected the migration of cortical neurons in the mouse brain. We further identified two common genes (Neurl4 and Usp39) affected by mutations of SETD1A. These results suggested that the mutations of SETD1A play a fundamental role in abnormal synaptic function and the development of neurons, so they may be pathogenic factors for neurodevelopmental disorders.
ABSTRACT
Objective To discuss the clinical value of using echocardiography to evaluate cardiac function in hypertension patients complicated with atrial fibrillation.Methods 60 hypertension patients complicated with atrial fibrillation were chosen as the observation group,and meanwhile 30 healthy subjects were chosen as the control group.Conventional two dimensional ultrasound was used to observe left front diameter (LAD),left ventricular end diastolic diameter (LVEDD),left ventricular end systolic diameter (LVESD) and left ventricular ejection fraction (LVEF).And mitral valve flow spectrum was also used to detect A peak and integral E-VTI E peak,A-VTI,and E/A,including the E peak deceleration time (DT).Pulmonary vein blood flow spectrum was used to detect systolic velocity (S),integral S-D-VTI,VTI,D peak,integral record systolic flow velocity (peak) Ar,and calculate the S/D value.Results In the observation group, LAD,LVEDD,LVESD,LAVmax and LAVmin were (43.01±2.34)mm,(48.87±4.35)mm,(30.29±4.34)mm,(42.38±3.55)mL and (20.22±2.35)mL, which were significantly higher than those in the control group [(34.23±2.10)mm,(43.23±4.30)mm,(24.34±4.12)mm,(31.04±3.10)mL and (14.57±2.19)mL], the differences were statistically significant (t=17.34,5.82,6.34,14.88 ,10.99,all P<0.05).In the observation group, the LVEF and TA-EF were (62.03±5.56)% and (58.66±5.45)%, which were significantly lower than those in the control group [(59.35±4.45)% and (52.34±4.68)%], the differences were statistically significant (t=2.30,10.99,all P<0.05).In the observation group, the E peak,E-VTI and E/A were (91.22±12.10)cm/s,(15.17±3.31) and (2.38±0.55) respectively, which were significantly higher than those in the control group [(71.28±12.11)cm/s,(12.21±3.30) and (0.92±0.30), t=7.37,4.04,13.54,all P<0.05].In the observation group, A peak,A-VTI and DT were (46.89±5.36)cm/s,(4.23±1.06) and (120.32±12.45),respectively, which were significantly lower than those in the control group [(79.44±6.12)cm/s,(7.85±1.15) and (234.37±13.49),t=25.89,14.84 ,39.84,all P<0.05].In the observation group, D peak and D-VTI were (53.80±5.76)cm/s and (14.20±1.56) respectively, which were significantly higher than those in the control group [(44.54±3.58)cm/s and (11.15±1.55),t=8.64,6.34,all P<0.05].In the observation group, Speak,S-VTI,S/D and Ar were (41.21±4.04)cm/s,(11.87±5.37),(0.78±0.09) and (21.34±3.05) respectively, which were significantly lower than those in the control group [(53.26±4.15)cm/s,(16.28±5.33),(1.29±0.13) and (38.57±3.89),t=12.12,3.94,21.75,23.00,all P<0.05].Conclusion Echocardiography can reflect the cardiac function in hypertension patients with atrial fibrillation.And assessing myocardial remodeling and atrial room to store the damage situation, pipeline and booster pump function all has important clinical significance for clinical treatment and prognosis assessment.