Clinical phenotype and genetic function analysis of a family with hypomyelinating leukodystrophy-7 caused by POLR3A mutation.

Hypomyelinating leukodystrophy (HLD) is a rare genetic heterogeneous disease that can affect myelin development in the central nervous system. This study aims to analyze the clinical phenotype and genetic function of a family with HLD-7 caused by POLR3A mutation. The proband (IV6) in this family mainly showed progressive cognitive decline, dentin dysplasia, and hypogonadotropic hypogonadism. Her three old brothers (IV1, IV2, and IV4) also had different degrees of ataxia, dystonia, or dysarthria besides the aforementioned manifestations. Their brain magnetic resonance imaging showed bilateral periventricular white matter atrophy, brain atrophy, and corpus callosum atrophy and thinning. The proband and her two living brothers (IV2 and IV4) were detected to carry a homozygous mutation of the POLR3A (NM_007055.4) gene c. 2300G > T (p.Cys767Phe), and her consanguineous married parents (III1 and III2) were p.Cys767Phe heterozygous carriers. In the constructed POLR3A wild-type and p.Cys767Phe mutant cells, it was seen that overexpression of wild-type POLR3A protein significantly enhanced Pol III transcription of 5S rRNA and tRNA Leu-CAA. However, although the mutant POLR3A protein overexpression was increased compared to the wild-type protein overexpression, it did not show the expected further enhancement of Pol III function. On the contrary, Pol III transcription function was frustrated (POLR3A, BC200, and tRNA Leu-CAA expression decreased), and MBP and 18S rRNA expressions were decreased. This study indicates that the POLR3A p.Cys767Phe variant caused increased expression of mutated POLR3A protein and abnormal expression of Pol III transcripts, and the mutant POLR3A protein function was abnormal.

Effects of parental rearing style on sleep problems in preschool children / 中国学校卫生

Objective@#To examine the effects of parental rearing style and its consistency on sleep problems of preschool children and to provide theoretical basis for making early family intervention measures.@*Methods@#A questionnaire survey was conducted among 2 744 children and their parents in 19 kindergartens in Anqing city. Parental Behavior Inventory (PBI) was used to investigate the rearing style of parents, and Chinese version of Children s Sleep Habit Questionnaire (CSHQ) was used to evaluate the incidence of sleep among preschoolers.@*Results@#Preschool children s overall rate of sleep disorder was 15.5%, and accompanied by sleep duration disorder (70.0%), sleep resistance (64.2%), sleep latency (38.7%), anxiety (15.5%), daytime sleepiness ( 10.1 %). Living in urban areas, parents smoking and drinking behaviors, and parents parenting style all affected preschoolers sleep ( P <0.05). Multivariate Logistic regression analysis showed that fathers active rearing style was negatively correlated with preschool children s sleep problems such as delayed sleep impedance and short sleep duration, while mothers active rearing style was negatively correlated with preschool children s sleep problems such as sleep resistance and night wake up ( P <0.05). There was a positive correlation between father s severe rearing style and preschoolers sleep resistance, sleep duration, short sleep disordered breathing, daytime sleepiness and total sleep problems, and mother s severe rearing style and preschoolers sleep duration, short sleep anxiety, night wakefulness, daytime sleepiness and total sleep problems ( P <0.05). Consistent rate of negative rearing patterns was a risk factor for short sleep duration in preschoolers ( OR =2.19，95% CI =1.12-4.28， P =0.02).@*Conclusion@#The detection rate of sleep problems in preschoolers is high. Parental supportive involvement has a positive effect on preschoolers sleep, while parental coercion hostile parenting has a negative effect on preschoolers sleep. The consistent rate of rearing styles affects the sleep duration of preschoolers.