暂无摘要。

With the rapid development of multimedia technology, the student centered flipped classroom model (FCM) and massive open online courses (MOOCs) have been increasingly introduced and implemented in higher medical education. However, comparative analyses of the offline face-to-face FCM and completely online FCM have been rarely reported. In this study, we focused specifically on a set of flipped classrooms in which prerecorded videos were provided before class. Using the Zhihuishu platform as the major online course platform, our team built a MOOC and evaluated the teaching effectiveness of the FCM in both the offline face-to-face class and the online electronic live class for medical genetics education. Questionnaires, paper-based and oral exams were used to collect data on the teaching effects of the different teaching methods. We found that student satisfaction and overall student performance in the offline FCM group was significantly higher than that in the completely online teaching group. Although online FCM allowed students to play back and review anywhere and anytime after class, students taught in offline FCM had a significantly higher degree of knowledge mastery, had a deeper understanding of theoretical knowledge, and were better at knowledge comprehensive application. The effects of their training on genetic disease clinical diagnosis and treatment skills were significantly better, and their capacity for scientific research was also significantly improved. Our research discussed the advantages of the online courses and the problems brought about by using these technologies, and it provided insight into online teaching practices in the era of internet-based medical education.

OBJECTIVE: Aggregating evidence convincingly establishes the predominant genetic basis underlying congenital heart defects (CHD), though the heritable determinants contributing to CHD in the majority of cases remain elusive. In the current investigation, BMP10 was selected as a prime candidate gene for human CHD mainly due to cardiovascular developmental abnormalities in Bmp10-knockout animals. The objective of this retrospective study was to identify a new BMP10 mutation responsible for CHD and characterize the functional effect of the identified CHD-causing BMP10 mutation.
METHODS: Sequencing assay of BMP10 was fulfilled in a cohort of 276 probands with various CHD and a total of 288 non-CHD volunteers. The available family members from the proband harboring an identified BMP10 mutation were also BMP10-genotyped. The effect of the identified CHD-causative BMP10 mutation on the transactivation of TBX20 and NKX2.5 by BMP10 was quantitatively analyzed in maintained HeLa cells utilizing a dual-luciferase reporter assay system.
RESULTS: A novel heterozygous BMP10 mutation, NM_014482.3:c.247G>T;p.(Glu83*), was identified in one proband with patent ductus arteriosus (PDA), which was confirmed to co-segregate with the PDA phenotype in the mutation carrier\'s family. The nonsense mutation was not observed in 288 non-CHD volunteers. Functional analysis unveiled that Glu83*-mutant BMP10 had no transactivation on its two representative target genes TBX20 and NKX2.5, which were both reported to cause CHD.
CONCLUSIONS: These findings provide strong evidence indicating that genetically compromised BMP10 predisposes human beings to CHD, which sheds light on the new molecular mechanism that underlies CHD and allows for antenatal genetic counseling and individualized precise management of CHD.

Medical genetics is a basic medical course that discusses the diagnosis, prevention and treatment of diseases in relation with genetic factors. This course requires students who have abilities of strong logical thinking, independent thinking, problem analyzing and solving. Single \"cramming\" teaching is difficult to mobilize students\' autonomous learning, and hardly achieves teaching effect of medical genetics. Teaching of case-based discussion breaks passive teaching mode in traditional class. The teacher throws out typically clinical cases. The students prepare materials around relevant problems of cases, and carry out class discussion. Then, key and difficult points of the course are integrated in teaching and learning interaction, which reaches a remarkable effect of teaching. Since 2013, the teaching and research group has carried out teaching of case-based discussion in undergraduates majoring in clinical medicine. In this paper, we screen and sort clinical cases on the basis of course teaching plan and case-based discussion in the teaching of medical genetics. The cases are summarized into 8 chapters in teaching case base, which basically cover the teaching of disease genetics and clinical genetics.The construction of teaching case base in medical genetics has realized the deep integration of clinical cases and teaching. Students can understand and master important and difficult points of teaching in a more intuitive way, which is helpful to stimulate students\' innovative thinking, improve students\' learning interest and class participation.
医学遗传学是探讨遗传因素相关疾病的诊断、预防与治疗的基础医学类课程，本门课要求学生具备较强的逻辑思维，有独立思考和分析解决问题的能力。单一的“填鸭式”课堂教学很难调动学生的自主学习，无法达到医学遗传学的教学效果。案例研讨式教学打破了被动的传统教学模式，教师给出临床典型案例，学生围绕案例的相关问题准备材料，主动展开课堂讨论，以教与学互动的方式融汇贯通了本门课程的重点与难点，教学效果显著。自2013年起，本教研组针对临床医学本科生开展了案例研讨式教学。本文根据课程的教学计划和案例研讨式教学的实际情况，筛选并分类整理了所收集的临床案例资料，分章节归纳汇编了8个章节的教学案例库，基本涵盖了疾病遗传学与临床遗传学的教学重难点。医学遗传学教学案例库的建设实现了临床案例与教学的深度融合，学生以更为直观的方式理解掌握教学重难点，有助于激发学生的创新思维，提高学生的学习兴趣与课堂参与度。.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients.

Medical genetics, which is a frontier subject in biomedicine, is the clinical core of gene diagnosis and gene therapy. In the training of medical students, medical genetics plays an important role in bridging basic medicine and clinical medicine. In recent years, problem-based learning (PBL) has been widely used in medical education as an important method to cultivate the autonomous learning ability of medical students. In the current study, we designed and shared the research on brachydactyly type A2 (BDA2) as the main case of PBL teaching, in order to guide the students towards autonomous learning, and to cultivate independent analysis and problem solving ability instead of simple knowledge acquisition. Such excellent academic teaching will provide more high quality medical talents and internationally competitiveness for constructing a healthy China.
医学遗传学是生物医学中的前沿学科，也是临床基因诊断和基因治疗的核心内容。在医学人才培养中，医学遗传学扮演着衔接基础医学与临床医学的重要角色。近年来，基于问题的学习(problem-based learning，PBL)作为培养医学生自主学习能力的重要方法，在医学教育中得到了广泛的应用。本文设计并分享了以A2型短指(趾)症(brachydactyly type A2，BDA2)研究为核心的PBL教学案例，以期引导学生自主学习，以能力培养代替知识传授，培养学生独立分析和解决问题的能力以及创新性思维的卓越学风，为健康中国建设输送更多具有国际竞争力的高素质医学人才。.

Congenital heart disease (CHD) represents the most frequent developmental deformity in human beings and accounts for substantial morbidity and mortality worldwide. Accumulating investigations underscore the strong inherited basis of CHD, and pathogenic variations in >100 genes have been related to CHD. Nevertheless, the heritable defects underpinning CHD remain elusive in most cases, mainly because of the pronounced genetic heterogeneity. In this investigation, a four-generation family with CHD was recruited and clinically investigated. Via whole-exome sequencing and Sanger sequencing assays in selected family members, a heterozygous variation in the SMAD4 gene (coding for a transcription factor essential for cardiovascular morphogenesis), NM_005359.6: c.285T > A; p.(Tyr95*), was identified to be in co-segregation with autosomal-dominant CHD in the entire family. The truncating variation was not observed in 460 unrelated non-CHD volunteers employed as control subjects. Functional exploration by dual-reporter gene analysis demonstrated that Tyr95*-mutant SMAD4 lost transactivation of its two key downstream target genes NKX2.5 and ID2, which were both implicated with CHD. Additionally, the variation nullified the synergistic transcriptional activation between SMAD4 and GATA4, another transcription factor involved in CHD. These data strongly indicate SMAD4 may be associated with CHD and shed more light on the molecular pathogenesis underlying CHD, implying potential implications for antenatal precise prevention and prognostic risk stratification of the patients affected with CHD.

BACKGROUND: As the most frequent type of birth defect in humans, congenital heart disease (CHD) leads to a large amount of morbidity and mortality as well as a tremendous socioeconomic burden. Accumulating studies have convincingly substantiated the pivotal roles of genetic defects in the occurrence of familial CHD, and deleterious variations in a great number of genes have been reported to cause various types of CHD. However, owing to pronounced genetic heterogeneity, the hereditary components underpinning CHD remain obscure in most cases. This investigation aimed to identify novel genetic determinants underlying CHD.
RESULTS: A four-generation pedigree with high incidence of autosomal-dominant CHD was enrolled from the Chinese Han race population. Using whole-exome sequencing and Sanger sequencing assays of the family members available, a novel SOX7 variation in heterozygous status, NM_031439.4: c.310C>T; p.(Gln104*), was discovered to be in co-segregation with the CHD phenotype in the whole family. The truncating variant was absent in 500 unrelated healthy subjects utilized as control individuals. Functional measurements by dual-luciferase reporter analysis revealed that Gln104*-mutant SOX7 failed to transactivate its two important target genes, GATA4 and BMP2, which are both responsible for CHD. In addition, the nonsense variation invalidated the cooperative transactivation between SOX7 and NKX2.5, which is another recognized CHD-causative gene.
CONCLUSIONS: The present study demonstrates for the first time that genetically defective SOX7 predisposes to CHD, which sheds light on the novel molecular mechanism underpinning CHD, and implies significance for precise prevention and personalized treatment in a subset of CHD patients.

Skeletal deformity is characterized by an abnormal anatomical structure of bone and cartilage. In our previous studies, we have found that a substantial proportion of patients with skeletal deformity could be explained by monogenic disorders. More recently, complex phenotypes caused by more than one genetic defect (i.e., dual molecular diagnosis) have also been reported in skeletal deformities and may complicate the diagnostic odyssey of patients. In this study, we report the molecular and phenotypic characteristics of patients with dual molecular diagnosis and variable skeletal deformities.
From 1108 patients who underwent exome sequencing, we identified eight probands with dual molecular diagnosis and variable skeletal deformities. All eight patients had dual diagnosis consisting of two autosomal dominant diseases. A total of 16 variants in 12 genes were identified, 5 of which were of de novo origin. Patients with dual molecular diagnosis presented blended phenotypes of two genetic diseases. Mendelian disorders occurred more than once include Osteogenesis Imperfecta Type I (COL1A1, MIM:166200), Neurofibromatosis, Type I (NF1, MIM:162200) and Marfan Syndrome (FBN1, MIM:154700).
This study demonstrated the complicated skeletal phenotypes associated with dual molecular diagnosis. Exome sequencing represents a powerful tool to detect such complex conditions.

Background Atrial fibrillation (AF) is the most common form of clinical cardiac dysrhythmia responsible for thromboembolic cerebral stroke, congestive heart failure, and death. Aggregating evidence highlights the strong genetic basis of AF. Nevertheless, AF is of pronounced genetic heterogeneity, and in an overwhelming majority of patients, the genetic determinants underpinning AF remain elusive. Methods and Results By genome-wide screening with polymorphic microsatellite markers and linkage analysis in a 4-generation Chinese family affected with autosomal-dominant AF, a novel locus for AF was mapped to chromosome 1q24.2-q25.1, a 3.20-cM (≈4.19 Mbp) interval between markers D1S2851 and D1S218, with the greatest 2-point logarithm of odds score of 4.8165 for the marker D1S452 at recombination fraction=0.00. Whole-exome sequencing and bioinformatics analyses showed that within the mapping region, only the mutation in the paired related homeobox 1 (PRRX1) gene, NM_022716.4:c.319C>T;(p.Gln107*), cosegregated with AF in the family. In addition, sequencing analyses of PRRX1 in another cohort of 225 unrelated patients with AF revealed a new mutation, NM_022716.4:c.437G>T; (p.Arg146Ile), in a patient. The 2 mutations were absent in 908 control subjects. Biological analyses in HeLa cells demonstrated that the 2 mutants had significantly diminished transactivation on the target genes ISL1 and SHOX2 and markedly decreased ability to bind the promoters of ISL1 and SHOX2 (2 genes causally linked to AF), although with normal intracellular distribution. Conclusions This study first indicates that PRRX1 loss-of-function mutations predispose to AF, which provides novel insight into the molecular pathogenesis underpinning AF, implying potential implications for precisive prophylaxis and management of AF.