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.

Prenatal diagnosis of spinal muscular atrophy using multiple ligation-dependent probe amplification / 中华医学遗传学杂志

OBJECTIVE@#To carry out prenatal diagnosis for families with high risk for spinal muscular atrophy (SMA) by using multiplex ligation-dependent probe amplification (MLPA).@*METHODS@#Twenty-one families were enrolled. MLPA was used to detect copy numbers of SMN1 and SMN2 genes. Maternal contamination was excluded by using a short tandem repeat method.@*RESULTS@#For 23 fetuses from the 21 families, 14 were identified as carriers, 1 as SMA patient, and 8 as normal. By linkage analysis of parental samples, three individuals were determined as silent (2+0) carriers.@*CONCLUSION@#MLPA can determine the carrier status of SMA. The identification of three silent (2+0) carriers among the 44 parental samples indicated a risk for such families, for which genetic counseling and reproduction guidance should be provided.

Advances in preimplantation genetic diagnosis / 中华内分泌代谢杂志

In the past 20 years,molecular genetic technology has developed rapidly.The leap forward development of single-cell genetic diagnosis technologies represented by whole genome amplification combined with microarray technology or next-generation sequencing not only increased the accuracy of preimplantation genetic diagnosis (PGD) but also greatly expanded the variety and scope of detectable diseases.This paper systematically reviews the clinical application of PGD as well as recent progress of related technologies.

The application of Raman spectroscopy in male reproduction diagnosis / 中华检验医学杂志

The limited method demands for new technology in the management of male infertility. Raman spectroscopy is a rapid and sensitive non-invasive diagnosing technology. Raman spectroscopy was able to obtain Raman spectra from individual human sperm cells and allows for the comparison of their biochemical components, DNA and mitochondrial structure as well as epigenetic changes. This review provided an overview of the principle of each major types and discussed the progress in clinical application , indicating the potential of Raman spectroscopy as an valuable addition in assessing the quality of sperm cells for in vitro fertilization.

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.

Detection of mosaic trisomy 9 missed by conventional cytogenetics using SNP-array and fluorescence in situ hybridization / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect mosaic trisomy 9 missed by conventional cytogenetics.</p><p><b>METHODS</b>Peripheral blood genomic DNA from a girl with mental retardation was analyzed using Affymetrix CytoScan (TM) HD array. Fluorescence in situ hybridization (FISH) was also performed on samples from two patients.</p><p><b>RESULTS</b>The SNP-array analysis has revealed multiple duplications along chromosome 9. FISH analysis showed that, for the peripheral blood sample from one patient, 40 of 100 interphase cells and 15 of 100 metaphase cells carried trisomy 9. For the cord blood sample from another patient, 35 of 100 interphase cells and 10 of 100 cultured cells carried trisomy 9.</p><p><b>CONCLUSION</b>SNP-array is useful for detecting low-level mosaicism which may be missed by conventional cytogenetics. Combined with karyotype and microarray analyses, FISH is a focused and targeted approach for diagnosing mosaic trisomy. They may provide a useful tool for differentiating pseudomosaicisms from true mosaicisms.</p>

Preimplantation genetic diagnosis of translocation / 中华妇产科杂志

Objectives To observe the genetic characteristics of chromosomes and the rates of implantation and pregnancy in couples of translocation carriers who undergo preimplantation genetic diagnosis (PGD) and to evaluate the significance of PGD in the treatment of translocation carriers. Methods Fluorescence in situ hybridization (FISH) was performed to analyze the embryos of 12 carriers of reciprocal translocation and 22 carriers of Robertsonian translocation. The results of diagnosis and the implantation and pregnancy rates were analyzed. Results A total of 253 embryos from 36 couples were retrieved and FISH was applied for the examination. The characteristics of chromosomes were diagnosed in 225 embryos and the rate of successful PGD was 88.9%. Fifty-eight embryos were found to have normal chromosome or balanced translocation and were transferred into the uterus. The rate of implantation was 36% (5/14) and 14% (6/44) and the rate of pregnancy was 4/9 and 26% (5/19) for carriers of Robertsonian translocation and reciprocal translocation, respectively. Conclusions The FISH-based PGD is effective in the diagnosis of Robertsonian translocation and reciprocal translocation of embryos. It provides the possibility of a high rate of implantation and pregnancy, and avoids recurrent abortion and unwilling termination of pregnancy.

CONTROLLED OVARIAN HYPERRSTIMULATION SIGNIFICANTLY DECREASED THE EXPRESSION OF AQUAPORIN-3 IN MOUSE OOCYTES USING SEMI-QUANTITATIVE REAL-TIME PCR ANALYSIS / 解剖学报

Objective To study the effect of controlled ovarian Hyperstimulation(COH)on expression of AQP3 mRNA in mouse oocytes at metaphase Ⅱ. Methods Twenty female mice(6-7 weeks) were randomly allocated into 2 groups, mice in COH group were superovulated by intraperitoneal injection of 7.5 IU pregnant mare's serum gonadotropin(PMSG) followed by 5 IU human chorionic gonadotropin(HCG) after 46-48?h. Nothing was given to mice in control group and the estrus cycle was observed at 9?am everyday. 12-16?h following hCG injection (COH group) or at 8?am next day after the estrus (control group), mice were killed by cervical dislocation. The oviducts were excised.Cumulus masses were recovered from the dilated ampullae under a dissecting microscope,digested granulosa cells using hyaluronidase. Semi-quantitative real-time PCR of AQP3 mRNA in mouse MⅡoocytes was investigated with ?-actin as the internal control. Results Oocytes swelling assay showed that AQP3 mRNA expressed in mouse MⅡ oocytes. Using semi-quantitative real-time PCR, the expression of AQP3 mRNA was significantly decreased(P