侧腭突生长发育和腭裂的分子调节机制

唇腭裂是一类常见的先天性畸形．可单独发生,也可与300多种已知的畸形伴发于综合征。唇腭裂又分为4型：综合征性唇裂伴或不伴腭裂（cleft of lip with or without palate,CL／P）、综合征性腭裂（cleft palat,CPO）、非综合征性唇裂伴或不伴腭裂（nonsyndromic cleft of lip with or without palate．nsCL／P）和非综合征性腭裂（nonsyndromic cleft palate．nsCPO）．     

转化生长因子α基因与非综合征性唇腭裂

非综合征性唇腭裂是一种复杂得多基因多因素遗传病，众多学者从候选基因和该病的关联性及基因间、基因环境间的相互作用方面进行了大量而广泛的研究。转化生长因子α是一种多肽类生长因子，促使细胞增殖和发生转化，小鼠的腭部融合时腭盖中部的上皮组织中含量较高，同时报道认为转化生长因子α等位基因同唇腭裂有联系，被作为非综合征性唇腭裂的候选基因之一。本文就转化生长因子α基因在唇腭裂发病中的作用的研究进展作一综述。     

非综合征型唇腭裂病因学研究进展

唇腭裂是常见的先天性疾病,在我国发病率为1.82‰[1].根据发生的原因,一般将唇腭裂分为两大类:综合征型唇腭裂(syndromic cleft lip and/orpalate,SCL/P)和非综合征型唇腭裂(nonsyndromic cleft lip and/or palate,NSCL/P);其中综合征型唇腭裂约占30％[2],为单基因疾病;非综合征型唇腭裂又分为单纯唇裂、单纯腭裂和唇腭裂3类,其发病多认为是由多基因控制并与环境因素相关.现就非综合征型唇腭裂病因学的研究进展进行综述.     

非综合征性唇腭裂的染色体基因位点研究进展

唇腭裂是常见的先天畸形之一,遗传因素在其发生中发挥着极其重要的作用.随着分子遗传学的发展,越来越多的易感基因被发现.本文就与非综合征性唇腭裂相关的染色体基因位点、与单纯性腭裂相关的染色体基因位点研究进展作一综述.     

非综合征性唇裂伴或不伴腭裂基因位点的研究

唇腭裂是一种常见的先天性畸形,其病因极其复杂。大量的研究表明基因在它的病因中占有很重要的地位。近年来利用分子生物学等技术方法寻找导致唇腭裂的基因位点,尤其是导致非综合征性唇裂伴或不伴腭裂的基因和位点,已初见端倪。本文对其研究现状进行综述。     

染色体基因位点与非综合征性唇腭裂致病机制的关系

非综合征性唇腭裂是人类最常见的先天性畸形之一,是一种多基因多因素的遗传疾病.近二十年来,学者们先后在多条染色体上发现了与非综合征性唇腭裂有关的基因位点.本文就染色体基因位点与非综合征性唇腭裂致病机制的关系作一综述.     

家族性非综合征性唇裂伴或不伴腭裂的基因研究

唇腭裂是一种常见的先天畸形，其发病率因国家，地区、种族的不同而有所不同。流行病学调查表明，国外新生儿唇腭裂发病率约为1‰，而在我国约为1．2％。其中，以非综合征形式存在的唇腭裂患者约有50％～70％，且有家族性发病的倾向。有家族史的单纯性腭裂(cleft palate only，CPO)和非综合征性唇裂伴或不伴腭裂患者(nonsyndromic     

唇腭裂的基因研究

唇腭裂是一种常见的先天畸形 ,有家族性发病倾向 ,文献报道单纯腭裂患者 (cleft palate only,CPO)有家族史的约 1 0 %～ 2 0 % ,非综合征性唇腭裂 (nonsyndromic cleft lip with or without cleftpalate,NSCL /P)有家族史的约 2 5%～ 35% [1] ,是为大家公认的一种多基因易感性疾病。由于唇腭裂的遗传模式并不符合孟德尔遗传模式 ,目前其遗传模式仍是个争论的话题 ,主要有两种 ,既多因素阈点模式以及近来提出的主要致病基因遗传模式 [2～ 4 ] ,而且唇腭裂因不同人种、地区、性别以及有无阳性家族史其发病率是不同的 ,因此唇腭裂的可能致…     

440例唇腭裂病人可疑发病因素分析

唇腭裂是最常见的先天畸形之一,发病率达0.182%,多数唇腭裂患者不伴发其他畸形,属非综合症性唇腭裂和或腭裂,并表现为多因素遗传模式[1]。多基因遗传的唇腭裂,除遗传因素外,环境因素也有影响,因此又称多因素遗传[2]。其病因尚不清楚,本文通过对临床收治的440例患者进行分?..     

1988～1992年中国非综合征性唇腭裂发生率的动态变化

目的　了解我国 1988～ 1992年非综合征性唇腭裂发生率的动态变化趋势及流行病学特征。方法　采用以医院为单位的整群抽样方法 ,对 1988～ 1992年期间我国 5 0 0多所医院孕 2 8周至产后 7天的 3 2 46 40 8例围产儿 ,4349例非综合征性唇腭裂病例进行回顾性分析。结果　我国 5年非综合征性唇腭裂发生率无显著性差异 ,城乡发生率也无显著性差异。男性发生率为 14.9/万 ,女性发生率为 11.7/万 ,差异有显著性 ,非综合征性唇腭裂的性别比为 1.3∶ 1。三类非综合征性唇腭裂各自的发生率为 :CL± P:7.8/万 ,CL:3.8/万 ,CP:1.8/万。结论　我国非综合征性唇腭裂发生率无变化趋势 ,城乡无差异。男性高于女性 ,唇裂合并腭裂为最常见类型。     

No evidence for a role of CRISPLD2 in non-syndromic cleft lip with or without cleft palate in an Italian population

Non-syndromic cleft lip with or without cleft palate (NSCLP) is a malformation with variable phenotypes, resulting from a mixture of genetic and environmental factors. Some studies have supported a role for the 16q24 region and its candidate gene, CRISPLD2, in clefting. A replication study is necessary to confirm these findings. The aim of the present study was to test, by genetic linkage and association analyses, whether the candidate gene, CRISPLD2, represents a risk factor for NSCLP. The analysis of 39 multigenerational families provided formal exclusion of a linkage between NSCLP and the CRISPLD2 locus under different genetic models and non-parametric analyses. The family-based study of 239 unrelated probands and their parents revealed no association between any particular allele or haplotype and NSCLP. Therefore, the present investigation did not support the hypothesis of the involvement of CRISPLD2 in NSCLP malformation, at least with regard to the Italian population.     

CRISPLD2 polymorphisms are associated with non‐syndromic cleft lip with or without cleft palate in a northern Chinese population

Shi J, Jiao X, Song T, Zhang B, Qin C, Cao F. CRISPLD2 polymorphisms are associated with non‐syndromic cleft lip with or without cleft palate in a northern Chinese population. Eur J Oral Sci 2010; 118: 430–433. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci Non‐syndromic cleft lip with or without cleft palate (NSCLP) is the most common craniofacial birth defect. This complex genetic disorder results from interactions between genes and environmental factors. Numerous genes have been reported in studies demonstrating association between the cleft lip and palate phenotypes and the alleles at single‐nucleotide polymorphisms (SNPs) within specific genes. Recently, the cysteine‐rich secretory protein LCCL domain containing 2 (CRISPLD2) has been revealed to be a novel candidate gene for NSCLP. The SNPs rs1546124, rs4783099 and rs16974880 in CRISPLD2 were highly significant in Caucasian and Hispanic multiplex families but showed no association in Colombian and Irish populations. In the current study, we examined these three SNPs in a northern Chinese population and found an association between these polymorphisms and NSCLP in both single‐marker and haplotype analyses. Our data further strengthen the conclusion that altered CRISPLD2 is associated with NSCLP susceptibility.     

Association study of single nucleotide polymorphisms of MAFB with non-syndromic cleft lip with or without cleft palate in a population in Heilongjiang Province,northern China

Non-syndromic cleft lip with or without cleft palate (NSCLP) is a common complex birth defect. MAFB (v-maf musculoaponeurotic fibrosarcoma oncogene homolog B) is a new gene that may be involved in susceptibility to cleft lip with or without cleft palate (CL/P). To further assess its role in NSCLP, we investigated 3 identified single nucleotide polymorphisms in MAFB (rs13041247, rs6065259, and rs11696257) and examined them for association with NSCLP in 344 patients and 324 healthy controls in a northern Chinese Han population with a high incidence of the syndrome. Peripheral blood samples were taken when patients enrolled in the study and DNA samples were extracted from the blood. The 3 single nucleotide polymorphisms were genotyped using a mini-sequencing method (Snapshot^® Multiplex System for SNP genotyping, Life Technologies Ltd, Paisley, UK). We found that rs6065259 was the most important single nucleotide polymorphism in MAFB (OR_6065259-AA = 0.45; 95% CI: 0.28 to 0.71; p = 0.0027), followed by rs13041247; however, no association was found between rs11696257 and NSCLP. Our study provides further evidence regarding the role of MAFB variations in the development of NSCLP in this northern Chinese Han population.     

Association of MSX1 799 G>T variant with nonsyndromic cleft lip/palate in South Indian adolescent patients

International Journal of Paediatric Dentistry 2012; 22: 228–231 Background. Nonsyndromic cleft lip/palate (NSCLP) is a common congenital anomaly with significant medical, psychological, social, and economic ramifications. It is an example of complex genetic trait. There is sufficient evidence to hypothesise that disease locus for this condition can be identified by candidate genes. The purpose of this study was to test whether MSX1 (799 G>T) gene variant was involved in the aetiology of NSCLP. Methods. Blood samples were collected with informed consent from 25 subjects having NSCLP and 25 controls. Genomic DNA was extracted from the blood samples, polymerase chain reaction was performed (PCR), and digestion products were evaluated. Results. The Results showed a positive correlation between MSX1 (799 G>T) gene variant and NSCLP patients. Conclusion. MSX1 (799 G>T) gene variants may be a good screening marker for NSCLP.     

Genes causing clefting syndromes as candidates for non‐syndromic cleft lip with or without cleft palate: a family‐based association study

Clefts of the orofacial region are among the most common congenital defects, caused by abnormal facial development during gestation. Non‐syndromic cleft lip with or without cleft palate (NSCLP) is a complex trait most probably caused by multiple interacting loci, with possible additional environmental factors. As facial clefts form part of more than 300 syndromes, one strategy for identifying the genetic causes of NSCLP could be to study candidate genes responsible for clefting syndromes. Three genes were selected for this investigation: TP63, which codes for the tumour protein p63 and causes Ectrodactyly‐Ectodermal dysplasia‐orofacial Cleft syndrome; JAG2, a downstream gene of TP63; and MID1, which is responsible for Opitz syndrome. A linkage disequilibrium investigation was performed with intragenic single nucleotide polymorphisms on each of these genes in a sample study of 239 patients/parents trios. Evidence which suggests that JAG2 and MID1 may play a role in NSCLP was obtained.     

Evaluating SKI as a candidate gene for non‐syndromic cleft lip with or without cleft palate

Non‐syndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common of all congenital malformations and has a multifactorial etiology. Findings in mice suggest that the v‐ski sarcoma viral oncogene homolog (SKI) gene is a candidate gene for orofacial clefting. In humans, a significant association between rs2843159 within SKI and NSCL/P has been reported in patients from the Philippines and South America. In the South American patients, the association was driven by the subgroup of patients with non‐syndromic cleft lip only (NSCLO). Here we investigated the association with rs2843159 in a Mayan Mesoamerican population (172 NSCL/P patients and 366 controls). In addition, we analyzed the phenotypic subgroups NSCLO and non‐syndromic cleft of lip and palate (NSCLP). A trend towards association between rs2843159 and NSCL/P was observed in the Mayan cohort (P = 0.097), and we found a stronger association in the NSCLP subgroup (P = 0.072) despite a limited sample size. To investigate whether other common variants within the SKI gene contribute to NSCL/P susceptibility in European and Asian populations, we also analyzed genotypic data from two recent genome‐wide association studies using set‐based statistical approaches. These analyses detected a trend toward association in the European population. Our data provide limited support for the hypothesis that common SKI variants are susceptibility factors for NSCL/P.     

Transverse craniofacial features and their genetic predisposition in families with nonsyndromic unilateral cleft lip and palate.

OBJECTIVE: The purpose of this study was to evaluate the transverse craniofacial form in families with nonsyndromic cleft lip and palate (NSCLP). It was hypothesized that affected as well as noncleft NSCLP family members are characterized by a common array of craniofacial features that differ from the general population. DESIGN: This was a prospective cross-sectional investigation that included affected children with NSCLP and their noncleft parents and siblings. PATIENTS, PARTICIPANTS: A total of 114 subjects (14 affected girls, 17 affected girls, 15 unaffected male siblings, 10 unaffected female siblings, 29 unaffected biological mothers, and 29 unaffected biological fathers) were included. Subject records comprised of posteroanterior cephalometric radiographs obtained from all 114 subjects. MAIN OUTCOME MEASURES: The width of midfacial structures, including the orbit and nose, was increased in NSCLP families, compared with published norms. Interestingly, the face was disproportionally wider in relation to total facial height. The transverse craniofacial form of children with or without clefts significantly correlated with that of their parents. Mothers displayed strong correlation with their affected and unaffected sons, whereas fathers correlated to their daughters, suggesting a possible sex-linked developmental influence. CONCLUSION: Better understanding of the genetic inheritance of craniofacial features associated with cleft lip and palate may ultimately contribute to the development of cleft risk assessment methods.     

BMP4、TGF-β3基因多态性与环境暴露在非综合征性唇腭裂发生中的交互作用

目的 探讨环境暴露因素、骨形态生成蛋白4(BMP4)基因、转化生长因子β3(transforming growth factor beta-3,TGF-β3)基因之间的交互作用在非综合征性唇腭裂(nonsyndromic cleft lip and cleft palate,NSCLP)发生中的可能作用.方法 通过问卷调查获取环境暴露资料.用聚合酶链反应(PCR)-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术对对照组(200例)和NSCLP组(200例)各基因位点的多态性进行检测.采用多因子降维法(multifactor djmensionality reduction,MDR)分析基因之间、基因与环境之间的交互作用关系,并对筛选的交互作用关系用Logistic回归进行验证.结果 BMP4 T538C、TGF-β3 C641A和TGF-β3G15572-三个单核苷酸多态性(single nucleotide polymorphism,SNP)位点间的交互作用与NSCLP的发生无关联.基因与环境交互作用分析发现,BMP4 T538C与母亲妊娠早期被动吸烟、母亲妊娠早期感染史对NSCLP的发生具有交互作用;TGF-β3G15572-与母亲妊娠早期被动吸烟、母亲妊娠早期感染史、父亲知晓妊娠前吸烟、父亲知晓妊娠前饮酒、母亲妊娠早期补充维生素对NSCLP的发生具有交互作用.经Logistic回归验证,结果一致.结论 NSCLP是基因与环境因素共同作用的结果,易感基因多态性影响着个体对环境因素的反应,研究它们之间的相互关系对阐明NSCLP的病因及发病机制具有重要意义.     

SUMO-1基因rs7580433多态性与非综合征性唇腭裂的关联研究

目的：研究SUMO-1基因rs7580433的多态性与中国人群非综合征性唇腭裂（NSCLP）的相关性。方法：从国际人类基因组单体型图计划（HapMap）选取来自中国北京汉族人群的多态位点rs7580433为研究位点,在183名NSCLP患者和162名健康正常人对此位点进行基因分型从而进行病例-对照研究。结果：NSCLP患者的GA基因型频率比正常对照组明显降低,其差异有统计学意义（P=0.025）。结论：SUMO-1基因rs7580433位点的基因多态性与中国人群NSCLP易感性相关。