遗传和表观遗传机制在先天性心脏病中的研究进展

先天性心脏病是胎儿期心脏及大血管发育异常所致的先天性畸形,是最常见的出生缺陷之一。先天性心脏病病因复杂,染色体异常、基因突变、核酸修饰、非编码RNA等遗传和表观遗传机制在其发生过程中发挥重要作用。现阶段,染色体异常、基因突变等遗传机制已经广泛应用于临床疾病的诊断与治疗。然而,针对遗传及表观遗传修饰在先天性心脏病的诊疗应用仍需深入研究。本文综述了染色体异常、基因突变、拷贝数变异及表观遗传修饰与先天性心脏病发生的关系,以期为进一步探究先天性心脏病早期诊断及个体化治疗提供依据。     

习惯性自发性流产女性的染色体结构稳定性研究

目的分析习惯性自发性流产女性和正常女性的染色体结构稳定性的不同,为提高生育质量提供理论依据。方法随机选择习惯性自发性流产的女性20人为观察组及正常的育龄女性20人为对照组,对其外周血淋巴细胞按姐妹染色单体互换(SCE)检测方法、微核检测方法及染色体断裂检测方法进行培养检测,分别记数SCE发生率、微核出现率及染色体断裂发生率。结果观察组的外周血淋巴细胞SCE发生率和微核出现率明显高于对照组(P<0.05);观察组的外周血淋巴细胞的染色体断裂发生率与对照组比较差异不明显(P>0.05)。结论SCE发生率和微核出现率可以作为经常暴露在易致DNA损伤的环境下发生习惯性自发性流产女性染色体结构稳定性的检测指标。     

273例曾生育非整倍体患儿父母染色体核型分析

目的：探讨曾生育非整倍体患儿父母染色体核型异常的检出情况。方法：利用G显带技术对273例曾生育非整倍体患儿父母以及116例健康体检者进行染色体核型分析,必要时加做C显带。结果：273例样本中共检出72例染色体变异,其中包括4例染色体结构异常,检出率为1.46%;68例染色体多态变异,检出率为24.91%;剔除高龄女性样本后,多态变异检出率为64/255（25.10%）。116例对照组染色体核型共检出1例染色体结构异常,5例染色体多态变异,多态变异检出率为4.31%,2组多态变异检出率差异有统计学意义（P＜0.05）。结论：曾生育非整倍体患儿父母染色体多态变异具有较高检出率,应引起临床医生的重视。     

银屑病患者淋巴细胞和角朊细胞染色体畸变及银屑病与乙型肝炎病毒的关系

为了明确银屑病患者血淋巴细胞和角朊细胞的染色体畸变情况及其与乙型肝炎病毒的关系，对１２例银屑病患者和１２例正常人的外周血淋巴细胞和角朊细胞进行了离体培养和ＤＮＡ抽提，用Ｇ显带方法作核型分析，用ＰＣＲ技术在各种标本中检测乙型肝炎病毒基因。结果表明，银屑病患者血淋巴细胞的非整倍细胞出现率明显高于角朊细胞和正常人血淋巴细胞，Ｇ显带技术发现１例患者的１个皮损角朊细胞中１１号染色体长臂２区３带发生断裂（１１ｑ２３：）；而银屑病患者血清、淋巴细胞、角朊细胞中均未检测到乙型肝炎病毒。提示：外周血淋巴细胞染色体的数目畸变在银屑病发病中起着一定的作用，银屑病患者淋巴细胞的染色体畸变、角朊细胞的增殖状态与乙型肝炎病毒基因之间没有必然关联     

UV‐induced Skin Cancer: Similarities – Variations

Skin cancer, the most common cancer world wide, encompasses different tumor entities, the keratinocyte‐derived basal cell carcinoma (BCC), and squamous cell carcinoma (SCC) as well as the neuroectodermal malignant melanoma (MM) and the neuroendocrine Merkel cell carcinomas (MCC). While knowledge is significantly increasing about genetic changes contributing to BCCs and MMs, our understanding for the development and progression of SCCs and MCCs is still fragmentary. This review, thus, aims, on the one hand to summarize the present knowledge without claiming completeness and, on the other hand, to provide information on the HaCaT in vitro skin carcinogenesis model that is used to evaluate the functional consequence of genetic aberrations believed to play a role in skin cancer development and progression.     

Beta-catenin is temporally regulated during normal liver development

BACKGROUND & AIMS: beta-Catenin, a key component of the Wnt pathway, plays an important role in unregulated liver growth in liver tumors, in regulated growth during liver regeneration, and in ex vivo embryonic liver cultures. METHODS: We used developing livers from several stages of gestational development to examine beta-catenin expression, protein-protein interactions, localization, and regulation in prenatal and postnatal livers. RESULTS: Microarray, Northern, and protein analyses showed peak expression of beta-catenin during early liver development at Embryonic day 10 (E10)-E12, followed by a decrease and a complete loss of normal beta-catenin (97-kilodalton species) after E16 through the remaining prenatal period. At the early stages, beta-catenin localized to the cytoplasm and nuclei of resident cells in addition to its normal membranous localization, which was seen at all later stages and in adult liver. Decreases in beta-catenin levels at E14 onward coincided with its decreased gene expression and increased degradation, as seen by an increase in serine 45/threonine 41-phosphorylated beta-catenin and its other negative regulators, such as axin, adenomatous polyposis coli gene product (APC), and glycogen synthase kinase-3 beta. Finally, we showed an intact association of E-cadherin and beta-catenin despite the loss of beta-catenin at E16-E18, owing to the presence of membrane-associated smaller-molecular-weight beta-catenin species. CONCLUSIONS: We also identified a stage-specific expression and regulation of beta-catenin during liver development that might be crucial for physiological liver development. Nuclear and cytoplasmic beta-catenin corresponded to cell proliferation in liver development. Finally, a smaller-molecular-weight species of beta-catenin might be maintaining normal interactions at the membrane.     

Dichorionic twin pregnancy with sirenomelia and chromosomal anomaly in 1 fetus: A case report

Rationale:Sirenomelia is a rare congenital malformation that threatens fetal survivals. The cases in which twin with sirenomelia and chromosomal abnormality have been seldomly reported. We reported a dichorionic twin case in which one twin had sirenomelia, the other twin had a normal phenotype, and they had different chromosomal abnormalities.Patient concerns:The abnormal twin was found at 22 weeks by ultrasound. The sirenomelia fetus was complicated with a thoracic stenosis, enlarged rectum without anal opening, the absence of bilateral kidneys, a single umbilical artery, a single lower limb, the abnormal curvature of spine, double outlet of right ventricle, which were the indicatives of the chromosome detection.Diagnosis:The copy number variation of the sirenomelia fetus was detected as a deletion of 4.8Mb in 11p11.12-11q11. The co-twin was found with del(Y)(q11.223q11.23), which was as the same as his father''s. The mother had normal chromosome. The parents had normal phenotypes. It was firstly reported a microdeletion with sirenomelia fetus.Interventions:There was no specific treatments for the twins.Outcomes:Intrauterine death of the sirenomelia fetus was found at 27 weeks and postnatal death after inevitable abortion happened to the co-twin.Lessons:Prenatal ultrasound was responsible for recognizing sirenomelia, and the detailed ultrasound scanning and chromosome detection should be done for the co-twin. The etiology of sirenomelia remains unclear, and genetic detection is also necessary for its pathogenesis research.     

The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with many CCRs, none of the reported mate-pair sequenced complex rearrangements have been simultaneously studied with state-of-the art molecular cytogenetic techniques. Here, we studied chromothripsis-associated CCR involving chromosomes 2, 5 and 7, associated with global developmental and psychomotor delay and severe speech disorder. We identified three truncated genes: CDH12, DGKB and FOXP2, confirming the role of FOXP2 in severe speech disorder, and suggestive roles of CDH12 and/or DGKB for the global developmental and psychomotor delay. Our study confirmes the power of MPS for detecting breakpoints and truncated genes at near nucleotide resolution in chromothripsis. However, only by combining MPS data with conventional G-banding and extensive fluorescence in situ hybridizations could we delineate the precise structure of the derivative chromosomes.     

胎儿颈后皮下积液内分隔与染色体异常的相关性

目的评估早孕期胎儿颈后皮下积液内分隔与染色体异常的关系。方法将2014年1月- 2016年12月早孕期超声检查提示颈项透明层(NT)增厚NT≥3 mm或颈后皮下积液出现分隔(NS)、接受侵入性产前诊断的胎儿281例纳入研究。将281例孕妇分为3组:NT厚度为3.0～5.0 mm且颈后皮下积液未发现分隔的胎儿(NT 3.0～5.0 mm组,n=124); NT厚度>5 mm且颈后皮下积液未发现分隔的胎儿(NT>5.0 mm组, n=96); 出现NS的胎儿(NS组,n=61)。结果NS组胎儿染色体异常率明显高于NT 3.0～5.0 mm组和 NT> 5 mm组( P<0.01)。经调整孕妇年龄、妊娠前体质量指数、种族、头臀长,NS组较NT 3.0～5.0 mm组( OR=4.97; 95% CI:2.76～10.77; P<0.01)和NT>5 mm组(OR=3.82; 95% CI:1.87～7.21; P<0.01)胎儿发生染色体非整倍体的风险更显著。结论颈后皮下积液是否存在分隔在妊娠早期染色体非整倍体筛查中可能可以作为一个有意义的筛查指标。