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Rare Mutations in SHROOM3 are Associated with Human Neural Tube Defects

Rare Mutations in SHROOM3 are Associated with Human Neural T...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Kuang Lele Wang Hongyan The State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Ant hropology & The Collaborative Innovation Centre of Genetics and Development School of Life ScienceFudan University Jiangwan Campus

Objective to explore the molecular mechanism and function of Shroom3 in human Neural tube d efects Method with the next generation whole exon sequencing,we sequenced the coding region of SH ROOM3 among all cases dan ***,lots of mutations were found including common(MA F>5%) and rare mutations(MAF<1%).As common mutations in human often don't have a good co nsistency with sides,and rare mutations play more and more important roles in NTD ***, we focus the de novo rare *** Sanger sequencing,we identify three case-specific nonsynonymous and one frameshift mutations in human ***,functional studies in vitro such as Co-IP and fluorescent colocalization were taken to explore the effect of mutations. Result In this study,363 miscarried of stillborn Han Chinese NTD fetuses from Jiangsu and Shan xi province, China were collected as *** group contains 215 unrelated normal fetuses born in the same ***,four rare case-specific heterozygous mutations were found in hum an *** vitro functional assays showed that all four mutations increased the interaction with D vl2,and lost the ability to inhibit PCP *** addition,Co-IP and fluorescent colocalization assa ys showed that frameshift mutation also disrupted its binding and colocalization with Rock1 SBD. Conclusion Apical constriction and convergent extension are the most critical processes during n eural tube ***3 mutations may act through PCP and Rock1 pathway together with ot her gene network and environment risk factors to mediate the severity of NTD phenotypes.

关键词： Rare Mutations in SHROOM3 are Associated with Human Neural Tube Defects

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Two de novo overlapping interstitial duplications at 10q22 associated with intellectual disability, developmental delay, speech impairments and behavior anomalies

Two de novo overlapping interstitial duplications at 10q22 a...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Yuan Haiming Liang Liyang Guangzhou kingmed center for clinical laboratory Co. Ltd. King Med School of Laboratory Medicine Guangzhou Medical University Sun Yat-Sen Memorial Hospital Sun Yat-Sen University

Objective Copy number variants(CNVs) involving chromosome 10 q22 region are rarely reported. At present, only seven patients with deletions at this locus have been reported. The reciprocal du plications are far more rare and have never been described. Method High-resolution chromosomal microarray analysis(CMA) was employed for our patients‘ tests. Result Here, we report two unrelated patients with de novo overlapping duplications at 10 q22.1 q22.3 interval detected by CMA. The CMA showed the two duplications : arr[hg19] 10 q22.1 q22.3(72,331,092-78,710,233)x3 dn and arr[hg19] 10 q22.1 q22.3(70,742,930-80,565,963)x3 dn respectively. Intellectual disability, developmental delay, speech impairments, distinctive facial features and behavior problems were observed in both patients. Conclusion The shared genomic region and the similar clinical features suggest a novel contiguo us gene duplication syndrome at 10 q22. Based on all pathogenic CNVs delineated and candidate genes identified in this interval, the critical region for the novel genomic duplication syndrome is l ocated on 10 q22.2 locus.

关键词： CMA Two de novo overlapping interstitial duplications at 10q22 associated with intellectual disability developmental delay speech impairments and behavior anomalies

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Effects of G6PD activity inhibition on the viability, migration and morphology of cervical cancer cells

Effects of G6PD activity inhibition on the viability, migrat...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Fang ZiShui Jiang ChengRui Feng Yi Chen RiXin Lin XiaoYing Zhang ZhiQiang Han LuHao Chen XiaoDan Li HongYi Guo YiBin Jiang WeiYing Sun Yat-sen University

Objective Glucose-6-phosphate dehydrogenase(G6 PD) deficiency has been revealed to be involved in the efficacy to anti-cancer therapy but the mechanism remains unclear. We aimed to investigate the anti-cancer mechanism of G6 PD deficiency. Method In our study, Dehydroepiandrosterone(DHEA) and sh RNA technology were used for inhibiting the activity of G6 PD of cervical cancer cells. Flow cytometry was used to detect the apoptosis and reactive oxygen species(ROS) generation. Scanning electron microscopy was used to observe cell morphology. And the migration rate of cell was also observed using the imaging system of inverted living cell microscope. Result When G6 PD was inhibited by DHEA or RNA interference, idioblasts were observed in He La cells. Simultaneously, G6 PD deficiency resulted in decreased He La cells migration and proliferation ability but increased ROS generation inducing apoptosis. What‘s more, the inhibition of G6 PD activity caused filopodia and reticulopodium of cells shorten and reduce as well as cells shrinkage. Conclusion Our results indicated the anti-cervix cancer mechanism of G6 PD deficiency may be involved with the decreased cancer cells proliferation caused by the increased ROS and decreased migration ability as a result of abnormal filopodia and reticulopodium of cells. Suppression of G6 PD may be a promising strategy in developing novel therapeutic methods for cervical cancer.

关键词： Effects of G6PD activity inhibition on the viability migration and morphology of cervical cancer cells

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A New Method for Measuring Autoimmune Disease Similarity by Integrating Semantic and Gene Functional Association and Network

A New Method for Measuring Autoimmune Disease Similarity by ...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Zhu Hongjie Henan Provincial People's Hospital

Objective Autoimmune disease is a polygenic complex disease and its pathogenesis is multifacet ed. So measuring similarity between diseases plays an important role in disease-related molecula r function research. However, it is still a challenge to calculate autoimmune disease similarity acc urately. Method Therefore, a new method that integrates network and semantic and functional associatio n is proposed to address the issue. First of all, Network Similarity is based on the topology charac teristics of the network which is constructed through genetic interaction. Functional Similarity is pr oposed to calculate disease similarity using disease-related gene sets in a weighted network of h uman gene function. Semantic Similarity is devised to calculate disease similarity using the relatio nship between two diseases based on the number of the genes associated with the disease. Fina lly, Net Sim and Fun Sim and Sem Sim are integrated to measure disease similarity. Result By this method we got the similarity relationship between autoimmune diseases, and built their networks and hierarchical clustering. And then through the application of hierarchical clusteri ng, the results showed that: four common autoimmune diseases(RA, MS, SLE, T1 D) showed a h igh similarity and were classified into the same cluster, which provided theoretical support for the study of their sharing mechanism and treatment;hemolytic anemia and Graves ophthalmopathy(t hyroid eye disease), having a high similarity, and literature had previously confirmed that the two diseases occurred in the same patient. Conclusion Construction of the network showed some autoimmune diseases presentation modul e of the network. These can help us understand the relationship between t autoimmune diseases from a global point of view, and provide us with the diagnosis and treatment of autoimmune diseases.

关键词： A New Method for Measuring Autoimmune Disease Similarity by Integrating Semantic and Gene Functional Association and Network

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A rare de novo interstitial duplication at 4p15.2 in a boy with severe congenital heart defects, limb anomalies, hypogonadism and global developmental delay

A rare de novo interstitial duplication at 4p15.2 in a boy w...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Yuan Haiming Xie Yingjun Guangzhou kingmed center for clinical laboratory Co. Ltd King Med School of Laboratory Medicine Guangzhou Medical University The third affiliated hospital of Guangzhou Medical University

Objective Proximal 4 p deletion syndrome is a relatively rare genetic condition characterized by dysmorphic facial features, limb anomalies, minor congenital heart defects, hypogonadism, cafeau-lait spots, developmental delay, tall and thin habitus and intellectual disability. At present, over 20 cases of this syndrome have been reported. However, duplication of reciprocal region of proximal 4 p deletion syndrome has never been reported. Here we report a 2-year-5-month-old boy with severe congenital heart defects, limb anomalies, hypogonadism, distinctive facial features, pre-and postnatal developmental delay and mild cognitive impairments. Method Chromosomal microarray analysis(CMA) and Next-generation sequencing(NGS) were employed for our patient‘s tests. Result A de novo 4.5 Mb interstitial duplication at 4 p15.2 p15.1 was detected by CMA, and NGS confirmed the duplication and revealed no additional pathogenic variants. Several candidate genes in this interval responsible for the complex clinical phenotypes were identified, such as RBPJ, STIM2, CCKAR and LGI2 genes. Conclusion The results suggest a novel contiguous gene duplication syndrome.

关键词： CMA NGS A rare de novo interstitial duplication at 4p15.2 in a boy with severe congenital heart defects hypogonadism and global developmental delay limb anomalies

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Identification and functional analysis of long non-coding RNAs in human and mouse early embryos based on single-cell transcriptome data

Identification and functional analysis of long non-coding RN...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Qiu Jia-jun Ren Zhao-rui Yan Jing-bin 上海市儿童医院

Objective Epigenetics regulations have an important role in fertilization and proper embryonic de velopment, and several human diseases are associated with epigenetic modification disorders, su ch as Rett syndrome, Beckwith-Wiedemann syndrome and Angelman syndrome. However, the d ynamics and functions of long non-coding RNAs(lnc RNAs), one type of epigenetic regulators, in human pre-implantation development have not yet been demonstrated. Method A comprehesive analysis of human and mouse early-stage embryonic lnc RNAs was perf ormed based on publlic single-cell RNA sequencing data. Result Expression profile analysis revealed that lnc RNAs are expressed in a developmental stag e–specific manner during human early-stage embryonic development, whereas a more temporalspecific expression pattern was identified in mouse embryos. Weighted gene co-expression netw ork analysis suggested that lnc RNAs involved in human early-stage embryonic development are associated with several important functions and processes, such as oocyte maturation, zygotic ge nome activation and mitochondrial functions. We also found that the network of lnc RNAs involved in zygotic genome activation was highly preservative between human and mouse embryos, wher eas in other stages no strong correlation between human and mouse embryo was observed. Conclusion This study provides insight into the molecular mechanism underlying lnc RNA involve ment in human pre-implantation embryonic development.

关键词： RNA Identification and functional analysis of long non-coding RNAs in human and mouse early embryos based on single-cell transcriptome data

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Identification and Clinical Implications of Novel MYO15A Mutations in a Non-consanguineous Chinese Family by Targeted Exome Sequencing

Identification and Clinical Implications of Novel MYO15A Mut...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Yan Tizhen Tang Ning Li Zhetao Li Wugao Tang Xiangrong Wang Lin Yang Yan Huang Jiwei Zheng Pei Cai Ren Zeng Dingyuan Key Laboratory of birth defects prevention and control Department of Medical Genetics Liuzhou Municipal Maternity and Child Healthcare Hospital Center of Hearing Liuzhou Municipal Maternity and Child Healthcare Hospital

Objective Autosomal recessive nonsyndromic hearing loss(ARNSHL) is a genetically heterogen eous sensorineural disorder, generally manifested with prelingual hearing loss and absence of ot her clinical manifestations. The aim of this study is to identify the pathogenic gene in a four-gener ation consanguineous Chinese family with ARNSHL. Method Two novel frame-shift mutations, c.5964+3 G>A and c.7395+1 G>A, in the myoxin XVa ge ne(MYO15 A) was identified by exome sequencing and Sanger sequencing. The compound heterozygous MYO15 A c.5964+3 G>A and c.7395+1 G>A variants co-segregated with the phenotypes in the ARNSHL family and was absent in one hund red normal controls. Result The variant was predicted to interfere with the formation of the Myosin XVa-whirlin-Eps8 c omplex at the tip of stereocilia, which is indispensable for stereocilia elongation. Our data suggest that the compound heterozygous MYO15 A c.5964+3 G>A and c.7395+1 G>A variants might be th e pathogenic mutation, and exome sequencing is a powerful molecular diagnostic strategy for AR NSHL, an extremely heterogeneous disorder. Conclusion Our findings extend the mutation spectrum of the MYO15 A gene and have important implications for genetic counseling for the family.

关键词： MYO Identification and Clinical Implications of Novel MYO15A Mutations in a Non-consanguineous Chinese Family by Targeted Exome Sequencing

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Whole-exome sequencing identifies two novel MARVELD2 frame-shift mutations as a cause of autosomal recessive nonsyndromic hearing loss in a Chinese family

Whole-exome sequencing identifies two novel MARVELD2 frame-s...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Yan Tizhen Cai Ren Tang Ning Li Wugao Li Zhetao Tang Xiangrong Luo Shiqiang Yang Yan Li Jingwen Wang Lin Zeng Dingyuan Key Laboratory of birth defects prevention and control Department of Medical Genetics Liuzhou Municipal Maternity and Child Healthcare Hospital Center of Hearing Liuzhou Municipal Maternity and Child Healthcare Hospital

Objective The genetic heterogeneity of hearing loss makes genetic diagnosis expensive and tim e consuming using available methods. Whole-exome sequencing has recently been introduced a s an alternative approach to identifying causative mutations in Mendelian disorders. Method To identify the hidden mutations that cause autosomal recessive nonsyndromic hearing l oss(ARNSHL), we performed whole-exome sequencing of a Chinese family with ARNSHL who w ere negative for GJB2 or SLC26 A4 mutations. Result We found two novel compound heterozygous frame-shift mutations, c.1360 del T and c.1507 del A, of MARVELD2 in the family with ARNSHL. Conclusion This is the first report of MARVELD2 frame-shift mutations in a Chinese population. We suggest that close attention should be paid to this gene when performing genetic testing of pa tients with hearing loss in China. The present results also indicate that whole-exome sequencing i s a valuable method for comprehensive medical diagnosis of a genetically heterogeneous recessi ve disease, especially in small-sized families.

关键词： frame Whole-exome sequencing identifies two novel MARVELD2 frame-shift mutations as a cause of autosomal recessive nonsyndromic hearing loss in a Chinese family

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10q26 deletion syndrome: two new cases and a review of the literature

10q26 deletion syndrome: two new cases and a review of the l...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Lin Shaobin Zhou Yi Luo Yanmin Fang Qun Chen Baojian Fetal Medicine Center Department of Obstetrics & Gynecology The First Affiliated Hospital of Sun Yat-Sen University

Objective We attempted to refine a CR for10 q26 deletion syndrome by performing a highresolution molecular analysis of two unrelated patients with pure terminal 10 q26 deletions. Method We report on two unrelated patients with similar clinical features, including craniofacial anomalies, developmental delay/intellectual disability and cardiac malformations, that are consistent with chromosome 10 q26 deletion syndrome. We compared these patients with patients with pure distal 10 q deletions described in CMA-based studies and the Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources(DECIPHER, https://***/). Result High-resolution single-nucleotide polymorphism analysis revealed that 10 q26 terminal deletions were present in these two patients. We compared the locations and sizes of the 10 q26 deletions in these two patients with the locations and sizes of 10 q26 deletions in 30 patients recorded in the DECIPHER database and 18 patients characterized in prior studies through chromosomal microarray analysis. We also reviewed the clinical features and locations of the 10 q26 deletions of these patients in an attempt to map or refine a critical region(CR) for phenotypes. Additionally, the relationship between previously suggested CRs and phenotypic variability was discussed. Conclusion We emphasize that a distal 10 q26 terminal deletion with a breakpoint at approximately 130.0 Mb could contribute to common clinical features of 10 q26 deletion syndrome.

关键词： deletion syndrome two new cases and a review of the literature

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Development of Bead-Based Suspension Array Technology for the Diagnosis of Hereditary Hearing Loss

Development of Bead-Based Suspension Array Technology for th...

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中华医学会第十五次全国医学遗传学学术会议暨中国医师协会医学遗传医师分会第一届全国学术会议暨2016年浙江省医学遗传学年会

作者： Liu Chang Zhang Liang Zhang Yan Ding Hongke Zhou Weiping Feng Defeng Zeng Yukun Liu Ling Yin Aihua Medical Genetic Centre Guangdong Women and Children Hospital Maternal and Children Metabolic-Genetic Key Laboratory Guangdong Women and Children Hospital

Objective Hearing loss is one of the most common birth defects and one of the most prevalent se nsorineural disorders. Given that hereditary hearing impairment exhibits incredible genetic hetero geneity, effective diagnostic methods are highly demanded by the clinical management. Method We developed a new diagnostic assay using the bead-based suspension array technolo gy(BBSAT), which can detect 20 point mutations in four genes of Asian prevalent hearing impair ment in parallel within 5 hours. More than 200 previously genotyped clinical samples were used t o determine the cut-off values and to validate the accuracy of new assay. Result In the BBSAT assay, suspended beads increase surface area to 3-D and more probes co ncentrated on beads. Besides, probes and targets mixed in the same mobile phase also generate better hybridization dynamics. With the multiplex PCR primer and probe design strategy, 20 point mutations in four genes of Asian prevalent hearing impairment can be simultaneously detected in a single assay. The results of BBSAT were completely in line with known genotypes, indicating th at the new diagnostic assay possesses excellent clinical sensitivity(100%) and specificity(100%) to identify genetic mutations of hearing loss. Conclusion The BBSAT is a rapid, accurate and cost-effective technology, suitable for molecular diagnosis of the hereditary hearing loss in large populations.

关键词： Development of Bead-Based Suspension Array Technology for the Diagnosis of Hereditary Hearing Loss

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