一个遗传性牙本质发育不全家系 DSPP基因的突变分析

目的 对1个遗传性牙本质发育不全家系进行临床表型分析和牙本质涎磷蛋白(dentin sialophosphoprotein,DSPP)基因突变检测。 方法 对家系成员进行全身基本情况及口腔专科检查,拍摄口内照、牙片及全景片;采集外周静脉血并提取DNA,用PCR扩增 DSPP基因的启动子及外显子,之后采用Sanger测序进行突变筛查,随后用PolyPhen-2和SIFT软件进行突变有害性预测,同时用Swiss-Port软件预测DSPP蛋白的三级结构。 结果 患者 DSPP基因第2外显子存在c.50C>T(p. P17L)杂合错义突变,其父亲也有此杂合突变,正常人群筛查未发现有突变者;该突变位于蛋白的高度保守区,有害性预测结果显示为有害,导致蛋白三级结构发生改变。 结论 DSPP基因突变是导致该家系发病的分子基础,这一结果拓展了 DSPP基因的突变谱,同时为该遗传性牙本质发育不全Ⅱ型家系的遗传咨询和产前诊断提供了理论依据。     

一个遗传性牙本质发育不全家系的分子遗传研究

目的 研究一个常染色体显性牙本质发育不全家系发病的遗传基础.方法 通过对一个DSPP家系临床检查和家族史调查,连锁分析和DSPP基因的突变检测,以及限制性片段长度多态分析方法,分析该家系发病的分子基础.结果 连锁分析发现,该疾病致病基因与微卫星标记D4S1534完全连锁,对位于该区域的DSPP基因进行测序分析,发现一个新的致病突变(c.49C→T,p.Pro17Ser),该突变位于DSPP基因的第1外显子.该家系所有患者中都检测到了这一致病突变,但家系中的正常个体和100个无亲缘关系的正常人中未发现这个突变.结论 p.Pro17Ser是牙本质发育不全Ⅱ型致病基因DSPP的一个新的致病突变.我们的研究进一步拓展了对牙本质发育不全疾病分子遗传基础的认识.     

一个颅骨锁骨发育不全家系的临床表型及遗传学分析

目的 探讨一个疑似颅骨锁骨发育不全(cleidocranial dysplasia,CCD)家系的临床特征和遗传学病因,为遗传咨询和产前诊断提供依据。 方法 收集8名家系成员的临床信息以及其中6人的外周血样,提取DNA。对先证者以及其他3位患病成员进行全外显子组测序,针对候选变异,在其他2位成员中进行Sanger测序验证。 结果 该家系4代共22人,其中8人患病,测序检测提示先证者携带 RUNX2基因[NM_001024630：c.1268_1277del(p.P425Afs*56)]致病变异,遗传自母亲,其他5名患病个体均携带该变异,而健康成员则未见相同的变异,基因型与表型存在共分离。 结论 RUNX2基因c.1268_1277del(p.P425Afs*56)变异可能是该CCD家系的遗传学病因,为临床诊治和产前诊断提供了依据。     

一个软骨发育不全家系成纤维细胞生长因子受体3基因突变分析

目的 基因水平上澄清一个不符合常染色体显性遗传病遗传规律的软骨发育不全家系患者的致病机理。方法 用聚合酶链反应技术扩增家系成员外周血基因组DNA成纤维细胞生长因子受体3(fibroblast growth factor receptor3，FGFR3)基因第10外显子，DNA序列分析寻找突变位点，然后经限制性内切酶Mae1分析验证。结果 患者外周血基因组DNAFGFR3基因第10外显子第1180位核苷酸发现一个A→T新突变，而家系正常成员包括先证者父母不存在此突变。结论 结合系谱分析，这一新突变可能是导致该家系患者软骨发育不全的原因。     

遗传性进行性肾炎一家系四代调查分析

遗传性进行性肾炎 (hereditaryprogressivenephritis)是一种严重的遗传性疾病 ,190 2年Guthrie首先提出了遗传性肾炎 ,192 7年Alport确定了它和耳聋的关系 ,故又名Alport’s综合征。现将一家系四代 2 1人中有 7人患遗传性进行性肾炎的结果报道如下。病例与家系先证者 (Ⅳ4) ,女 ,4岁 ,以血尿、少尿、全身浮肿 4个月为主诉 ,有双耳流脓史 ,查体 ,血压 135 /85mmHg ,面色苍黄 ,神志清楚 ,全身明显浮肿 ,呈凹陷性 ,轻度斜视 ,心肺阴性 ,腹稍隆 ,肝脾未及 ,腹部叩诊移动性浊音可疑 ,双肾无叩击痛 ,尿常规蛋白 ++、RBC++++/Hp ,颗粒管型 0～ …     

FGFR3基因突变分析鉴别软骨发育不全及类似遗传性侏儒

目的 了解中国人软骨发育不全患者（ａｃｈｏｎｄｒｏｐｌａｓｉａ,ＡＣＨ）的基因突变情况,建立一种快速简便的从分子水平鉴别ＡＣＨ及类似遗传性侏儒的方法。方法 对２１例ＡＣＨ患者及６例颖似ＡＣＨ患者的干血滤纸片进行成纤维细胞成长因子受体３（ｆｉｂｒｏｂｌａｓｔ ｇｒｏｗｔｈ ｆａｃｔｏｒ ｒｅｃｅｐｔｏｒ３,ＦＧＦＲ３）基因跨膜区特异性扩增,通过限性内切酶分析、单链构象多态和变性梯度凝胶电泳检测基因突     

遗传性耳聋一家系分析

通过对非综合性耳聋患者家系的聋基因热点突变的筛查,是防控遗传性耳聋的首要步骤。在此基础上再结合用药指导、产前诊断、临床干预可有效减少耳聋的发生。     

遗传性多毛症一家系报告与分析

作者等几年前，在内部资料中介绍过一遗传性多毛症家系．现增加讨论内容，特发表提供资料，供参考。     

遗传性视神经萎缩、白化病一家系调查

遗传性视神经萎缩是线粒体遗传病 ,白化病为常染色体隐性遗传病 ,作者在遗传咨询中发现一家系五代中有 12例视神经萎缩患者 ,2例白化病患者 ,现报告如下。病例与家系先证者Ⅲ9,男 4 5岁 ,于 7年前在建筑工地劳动中 ,突感视物不清 ,眼前似有雾 ,无疼感 ,随到市医院做诊治 ,见结膜无充血 ,无异物 ,双侧瞳孔等大等圆 ,眼底检查示视乳头血管膨胀 ,颜色苍白 ,乳头水肿。给予阿托品 ,VitB1、VitB12 等药物治疗半月效果不佳 ,视力渐退 ,出院诊断遗传性视神经萎缩 ,一月后视力仅存光感 ,持续至今。Ⅲ9的父母为近亲结婚 ,调查本家系五代共有 11名与…     

遗传性牙本质发育异常的分子遗传学研究进展

遗传性牙本质发育异常(hereditary dentin defect)是一种常染色体显性遗传性疾病,其发病率为1/10 000～1/6 000不等。牙本质发育异常主要分为2类,一类为牙本质发育不良(dentin dysplasia,DD),包括DD-Ⅰ和DD-Ⅱ;另一类为牙本质发育不全(dentinogenesis imperfect,DGI),包括DGI-Ⅰ、DGI-Ⅱ和DGI-Ⅲ。目前已基本明确了DGI-Ⅰ、DGI-Ⅱ、DGI-Ⅲ和DD-Ⅱ的致病基因和发病机制,DD-Ⅰ的致病基因研究也有了新的进展。本文对这5个类型的遗传性牙本质发育异常的研究现状作一综述。     

遗传性出血性毛细血管扩张症基因突变分析

目的 分析遗传性出血性毛细血管扩张症(hereditary hemorrhagic telangiectasia,HHT)家系ENG、ACVEL1和SMAD4基因突变.方法 收集4个HHT家系临床资料并分析其临床特点,应用直接测序和多重连接探针扩增技术对11例临床确诊及可疑患者的ENG、ACVRL1和SMAD4基因进行突变分析,将结果与HHT基因突变数据库进行对比.结果 家系2先证者及2个妹妹的ENG基因发生了第2外显子c.207G＞A(p.L69L)同义突变、第8外显子c.1004A＞T(p.Q335L)错义突变、ACVRL1基因第7外显子c.817C＞T(L273L)同义突变;家系3先证者及其母亲和弟的ENG基因发生了第8外显子c.1004A＞T(p.Q335L)突变;也检测到家系4先证者及其兄的ENG基因第8外显子c.1004A＞T(p.Q335L)突变.家系1先证者及其他HHT患者,未检测到基因突变.其中ENG基因第8外显子c.1004A＞ T(p.335Q＞L)为新突变,在200名正常对照中也未检测到该突变.结论 HHT具有遗传异质性,ENG基因第8外显子c.1004A＞T(p.Q335L)为HHT新的致病突变.     

Anxiety and depression among subjects attending genetic counseling for hereditary cancer

OBJECTIVES: The main aims of the study were to investigate changes in anxiety and depression over time in subjects attending genetic counseling (GC) for hereditary cancer, and secondly, to identify psychological, social, and medical variables associated with the course and outcome of anxiety and depression. METHODS: Of 275 eligible individuals, 221 consented to participate, 214 returned the baseline questionnaire, and were included in a prospective multi-center study. Questionnaires were mailed to the subjects before and after the GC. RESULTS: The mean values for anxiety and depression were quite low at all assessments. Mixed linear analyzes revealed that both anxiety and depression declined over time. Higher age, GC-related self-efficacy, and social support were associated with lower levels of anxiety. More social support, satisfaction with GC, self-rated physical function, and GC-related self-efficacy were associated with lower levels of depression. The effects of social support on both anxiety and depression had a significant interaction with time. CONCLUSION: The results support the buffer theory, which proposes that social support acts as a buffer, protecting people from the potentially pathogenic influence of stressful life events, such as GC. PRACTICE IMPLICATIONS: Subjects with less social support and less GC-related self-efficacy seem to be more vulnerable to anxiety and depression and should be offered extra attention by counselors.     

一个遗传性脊髓小脑型共济失调大家系的致病基因分析

目的探讨一个遗传性脊髓小脑型共济失调（SCA）大家系的遗传特点和基因突变分析。方法对一个遗传性脊髓小脑型共济失调（SCA）大家系进行家系调查,绘制系谱图,抽取家系成员外周血,采用聚合酶链反应和毛细管电泳对致病基因进行分析检测。结果该家系的遗传性脊髓小脑型共济失调（SCA）为常染色体显性遗传,6代45人中有15人为SCA患者,4人为携带致病基因的无症状患者。患者ATX3基因的CAG三核苷酸重复65-73次。结论该家系为常染色体显性遗传的SCA3型（SCA/MJD）,患者基因突变检测分析显示异常扩增的CAG突变数与发病年龄呈明显的负相关。基因突变检测在疾病诊断和早期发现无症状患者方面有重要作用,从遗传生殖角度阻断该病的遗传有重要意义。     

Taurodontism and enamel hypomaturation associated with X-linked abnormalities

The association of taurodontism with hypoplastic/hypomature enamel defects is presented in two cases of X-chromosome aneuploidy (47,XXY) and one of X-linked recessive Amelogenesis Imperfecta. It appears that the X-chromosome not only plays some role in tooth size the degree of taurodontism increasing with increased number of X chromosomes), but probably also plays a role in enamel maturation.     

假肥大型肌营养不良症基因诊断及遗传分析

目的对假肥大型肌营养不良症（DMD／BMD）患者进行基因诊断并对家系进行遗传分析,以提高对DMD／BMD的基因诊断水平及有效的遗传咨询。方法对40例DMD／BMD患者应用18对引物多重PCR技术进行Dystrophin基因缺失诊断,收集完整家系资料进行遗传分析以判断致病基因携带者及评估风险。结果40例DMD／BMD患者基因诊断有27例至少存在一个外显子片段缺失（67．5％）,13例未检测到缺失（32．5％）。通过对家系的遗传分析判断出致病基因携带者。结论多重PCR作为一种简便快速的诊断方法可对DMD／BMD患者进行基因诊断;对风险家系进行遗传分析、判断致病基因携带者以进行有效的遗传咨询,进而控制遗传病。     

Genome-wide linkage analysis and mutation analysis of hereditary congenital blepharoptosis in a Japanese family

Hereditary congenital ptosis (PTOS) is defined as drooping of the upper eyelid without any other accompanying symptoms and distinguished from syndromic blepharoptosis. Two previous linkage analyses assigned a PTOS locus (PTOS1) to 1p32-p34.1 and another (PTOS2) to Xq24-q27.1. In addition, in a sporadic case with a balanced chromosomal translocation t(1;8) (p34.3;q21.12), the ZFHX4 (zinc finger homeodomain 4) gene was found to be disrupted at the 8q21.12 breakpoint, but there was no gene at the 1p34.3 breakpoint, suggesting the existence of the third PTOS locus (PTOS1) at 8q21.12. We carried out a genome-wide linkage analysis in a Japanese PTOS family and calculated two-point and multipoint log of odds (LOD) scores with reduced penetrance. Haplotype analysis gave three candidate disease-responsible regions, i.e., 8q21.11-q22.1, 12q24.32-q24.33, and 14q21.1-q23.2. Although the family size is too small to define one of them, 8q21.11-q22.1 is a likely candidate region, because it contains the previously reported translocation breakpoint above. We thus performed mutation, Southern-blot and methylation analyses of ZFHX4 but could not find any disease-specific change in the family. Nevertheless, our data may support the localization of PTOS1.     

Hierarchical modelling of in situ elastic deformation of human enamel based on photoelastic and diffraction analysis of stresses and strains

Human enamel is a typical hierarchical mineralized tissue with a two-level composite structure. To date, few studies have focused on how the mechanical behaviour of this tissue is affected by both the rod orientation at the microscale and the preferred orientation of mineral crystallites at the nanoscale. In this study, wide-angle X-ray scattering was used to determine the internal lattice strain response of human enamel samples (with differing rod directions) as a function of in situ uniaxial compressive loading. Quantitative stress distribution evaluation in the birefringent mounting epoxy was performed in parallel using photoelastic techniques. The resulting experimental data was analysed using an advanced multiscale Eshelby inclusion model that takes into account the two-level hierarchical structure of human enamel, and reflects the differing rod directions and orientation distributions of hydroxyapatite crystals. The achieved satisfactory agreement between the model and the experimental data, in terms of the values of multidirectional strain components under the action of differently orientated loads, suggests that the multiscale approach captures reasonably successfully the structure–property relationship between the hierarchical architecture of human enamel and its response to the applied forces. This novel and systematic approach can be used to improve the interpretation of the mechanical properties of enamel, as well as of the textured hierarchical biomaterials in general.     

Relationship of Phenotype and Genotype in X-Linked Amelogenesis Imperfecta

X-linked amelogenesis imperfectas (AI) resulting from mutations in the amelogenin gene (AMELX) are phenotypically and genetically diverse. Amelogenin is the predominant matrix protein in developing enamel and is essential for normal enamel formation. To date, 12 allelic AMELX mutations have been described that purportedly result in markedly different expressed amelogenin protein products. We hypothesize that these AMELX gene mutations result in unique and functionally altered amelogenin proteins that are associated with distinct amelogenesis imperfecta phenotypes. The AMELX mutations and associated phenotypes fall generally into three categories. (1) Mutations (e.g., signal peptide mutations) causing a total of loss of amelogenin protein are associated with a primarily hypoplastic phenotype (though mineralization defects also can occur). (2) Missense mutations affecting the N-terminal region, especially those causing changes in the putative lectin-binding domain and TRAP (tyrosine rich amelogenin protein) region of the amelogenin molecule, result in a predominantly hypomineralization/hypomaturation AI phenotype with enamel that is discolored and has retained amelogenin. (3) Mutations causing loss of the amelogenin C terminus result in a phenotype characterized by hypoplasia. The consistent association of similar hypoplastic or hypomineralization/hypomaturation AI phenotypes with specific AMELX mutations may help identify distinct functional domains of the amelogenin molecule. The phenotype-genotype correlations in this study suggest there are important functional domains of the amelogenin molecule that are critical for the development of normal enamel structure, composition, and thickness.     

烤瓷牙用白榴石晶体的合成

本文研究了合成白榴石晶体的方法。研究了熔制玻璃的配方，热处理温度和时间对试样热膨胀系数大小的影响。当玻璃的配方越接近白榴石的理论成分点时，经热处理后试样的热膨胀系数越大，说明从玻璃中析出的白榴石晶体越多。对此种成分的玻璃在７００℃热处理２小时以上，可以获得最大的膨胀系数。对热处理后的玻璃进行Ｘ光衍射表明，其析出的是白榴石晶体，并对其进行了偏光显微镜观察，检定。     

The pathophysiology of hereditary angioedema

Regulatory T cells (Tregs) have been shown to be critical in the balance between autoimmunity and tolerance and have been implicated in several human autoimmune diseases. However, the small number of Tregs in peripheral blood limits their therapeutic potential. Therefore, we developed a protocol that would allow for the expansion of Tregs while retaining their suppressive activity. We isolated CD4+CD25 hi cells from human peripheral blood and expanded them in vitro in the presence of anti-CD3 and anti-CD28 magnetic Xcyte Dynabeads and high concentrations of exogenous Interleukin (IL)-2. Tregs were effectively expanded up to 200-fold while maintaining surface expression of CD25 and other markers of Tregs: CD62L, HLA-DR, CCR6, and FOXP3. The expanded Tregs suppressed proliferation and cytokine secretion of responder PBMCs in co-cultures stimulated with anti-CD3 or alloantigen. Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or graft-versus-host disease.