Biallelic variants in RBM42 cause a multisystem disorder with neurological, facial, cardiac, and musculoskeletal involvement

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.

Effect of Mindfulness-based Stress Reduction on Perceived Stress and Mental State of Patients with in Vitro Fertilization / 现代生物医学进展

Objective:To investigate the effect of Mindfulness-based stress reduction (MBSR) on perceived stress and mental state of patients with in vitro fertilization.Methods:83 cases women who were assisted reproduction with in vitro fertilization and embryo transfer (IVF-ET) in our hospital from May 2014 to December 2016 were selected as research objects.All the subjects were divided into control group and observation group according to the random number table method,with 41 cases in the control group and 42 cases in the observation group.Patients in the control group were given routine comprehensive nursing intervention,while the observation group was given MBSR intervention on the basis of the control group.The scores of self rating depression scale (SDS),self rating anxiety scale (SAS) and Chinese perceived stress scale (CPSS) before and after the intervention in the two groups were compared.Results:There was no significant difference in SDS score,SAS score and CPSS score between the two groups before intervention (P＞0.05).The scores of SDS,SAS and CPSS in observation group after intervention were (43.53± 4.89),(42.38± 4.34) and (27.53± 4.89),which were lower than (57.96± 7.30),(56.42± 5.49),(37.96± 7.30) before intervention,and the differences were statistically significant (P＜0.05).The scores ofSDS,SAS and CPSS in control group after intervention were (51.13± 5.52),(51.13± 5.52) and (31.13± 5.52),which were lower than (58.83± 7.28),(56.45± 5.51),(38.83± 7.28) before intervention,and the differences were statistically significant(P＜0.05).And those scores in were lower in observation group than in control group,the differences were statistically significant (P＜0.05).Conclusion:MBSR intervention can effectively improve the anxiety,depression and perceived stress of patients with in vitro fertilization,which is helpful in improving the success rate of IVF-ET,and it is worthy of clinical application.