一例Van der Woude 综合征家系IRF6基因突变的检测

目的 :对一例河北峪金矿VanderWoude综合征 (VWS)家系进行IRF6基因突变的检测。方法 :在IRF6(interferonregulatoryfactor 6)基因内设计引物 ,经分段聚合酶链反应 (PCR)和DNA测序进行突变检测 ,运用PIX ProteinIdentification软件对检测结果进行蛋白质二级结构分析。结果 :在所有患者IRF6基因的第 40 0密码子发现与表型一致的CGG >TGG (r .14 61c→t)的突变 ,该突变引起IRF6蛋白质二级预测结构的改变。结论 :VanderWoude综合征由IRF6基因突变引起 ,IRF6基因与唇腭、牙齿发育密切相关。     

1个河南van Der Woude综合征家系IRF6基因的突变检测

目的:对1个河南省vanDerWoude综合征(VWS)家系进行IRF6基因的突变检测。方法:在IRF6(interferonregulatoryfactor6)基因内设计引物,经分段PCR(聚合酶链反应)和DNA测序,进行突变检测,运用PIX-ProteinIdentification软件对检测结果进行蛋白二级结构分析。结果:在该家系所有患者IRF6基因的第6密码子,均发现与表型一致的CGC>TGC(r.279c→t)突变,该突变引起IRF6蛋白二级预测结构的改变。结论:vanDerWoude综合征由IRF6基因突变引起,IRF6基因与唇、腭、牙的发育密切相关。     

一个腘翼综合征(PPS)家系IRF6基因的突变检测

目的：对一个Guo翼综合征(popliteal pterygium syndrome，PPS)家系进行IRF6基因的突变检测。方法：在IRF6(interferon regulatory factor6)基因内设计引物扩增编码区及其邻近剪接内含子序列，经分段PCR(聚合酶链反应)和DNA测序进行突变检测。结果：在IRF6基因没有发现与表型一致的突变。结论：该PPS综合征可能由非编码区的IRF6基因突变引起或可能存在异质性。     

一个陕西汉族Van der Woude综合征家系IRF6基因的突变筛查

目的对一个陕西省汉族Van der Woude综合征(VWS)家系进行IRF6基因的突变筛查.方法在IRF6(interferon regulatory factor 6)基因内设计引物,经分段PCR(聚合酶链反应)包括剪切位点的9个外显子后DNA测序进行突变筛查,运用PIX-Protein Identification软件对检测结果进行蛋白二级结构分析.结果在所有患者IRF6基因的第2密码子发现与表型一致的GCC>GTC (r.268c→t NM 214278)的突变,该突变引起IRF6蛋白二级预测结构的改变.结论该家系Van der Woude综合征由IRF6基因突变引起,IRF6基因与唇腭、牙齿发育密切相关.     

一个范德伍德综合征家系的IRF6基因突变检测

目的:对收集的1个湖北Van der Woude综合征(VWS)家系进行临床和遗传特点分析,并进行IRF6基因的突变检测。方法:通过先证者及现场家系调查、临床检查和系谱分析收集VWS家系。在IRF6基因的外显子-内含子接头及9个外显子编码区分别设计引物,经聚合酶链式反应扩增并纯化后直接测序。结果:收集的VWS家系符合常染色体显性遗传特征,家系受累患者共3名(1名男性和2名女性),患者表现为典型的下唇瘘管或凹陷,且合并有唇腭裂和先天缺牙。患者表型在同一家系内有明显差异,且呈逐代加重趋势。在所有患者IRF6基因第412位密码子发现与表型一致的CGA>TGA(c.1234C>T)改变,经查证为一个已知的无义突变。结论:该VWS家系疾病表现度极不一致,是由IRF6基因的1个已知无义突变导致,IRF6是参与颌面部发育的重要基因。     

Rieger综合征-附1例家系病例报告

目的：分析1例Rieger综合征的典型家系病例，对临床医师认识和诊断这一与口腔发育异常密切相关的罕见遗传病提供线索和信息。方法：对1例Rieger综合征患进行家系调查，对家系成员进行临床检查，修复治疗和表型分析。结果：临床诊断1例Rieger综合征病例家系，显示常染色体显性的遗传方式，该综合征可导致严重的上颌骨发育不足和多数恒牙先天缺失。结论：Rieger综合征是导致先天性牙齿缺失的重要遗传性疾病之一，由于修复治疗的需要，可能对口腔医师在这一疾病的发现和诊断中起到重要作用。     

Van der Woude综合征家系先天缺牙患者MSX1基因突变的检测

目的探讨MSX1基因与Van der Woude综合征(VWS)家系中缺牙的关系。方法从VWS家系9中伴发缺牙患者2人及家系正常成员2人、60个牙列完整的健康者共64人的静脉血中提取DNA,设计MSX1基因引物,采用PCR方法扩增MSX1基因外显子1、2的编码区,而后对外显子1、2的PCR纯化产物测序,进行序列比对分析。结果 VWS家系9两个缺牙患者MSX1基因中有ivs2+68 C>T多态;伴IRF6基因突变的VWS患者缺牙较多。结论 VWS家系9中先天缺牙患者的牙先天缺失与MSX1基因的ivs2+68 C>T多态可能相关。     

中国人群非综合征性唇腭裂患者IRF6基因突变检测

目的 探讨干扰素调节因子6(interferon regulatory factor 6, IRF6) 在非综合征性唇腭裂(non-sydromic cleft lip and/or cleft palate,NSCL/P)患者中的突变情况。方法：收集119例NSCL/P患者及288名健康人对照样本的外周血血样并提取DNA。在IRF6基因的全部外显子分别设计引物,PCR扩增其序列,通过测序找出IRF6基因突变,并将这些突变在对照样本中进行验证。结果：共发现5种在正常人中没有的突变,其中4种是新发现的突变。结论：IRF6基因突变在中国人群中参与了非综合征唇腭裂疾病的发生。     

少汗型外胚层发育不良综合征1例

报告1例少汗型外胚层发育不良综合征.临床检查:患儿全身毛发稀疏;口内检查:混合牙列,牙列缺损,牙槽嵴发育不良.诊断为少汗型外胚层发育不良综合征,并采用可摘局部义齿修复治疗,咀嚼功能恢复良好.     

痣样基底细胞癌综合征家系1例

痣样基底细胞癌综合征是一种罕见的常染色体显性遗传病,以发育异常和肿瘤发生为主要临床特征。本文报告1例痣样基底细胞癌综合征家系,并结合相关文献对该病的发病率、发病机制、临床表现、治疗方法等进行讨论。     

Treatment of lower lip pits in Van der Woude syndrome: a systematic review

The presence of lower lip pits in individuals with Van der Woude syndrome (VWS) may cause discomfort due to saliva secretion. Furthermore, one of the main complaints in relation to lip pits is poor aesthetics, which often affects quality of life. The aim of this systematic review was to identify the best technique for the surgical removal of lower lip pits in terms of aesthetic and functional characteristics. A search of the PubMed, Embase, Web of Science, Science Direct, and Scopus databases was performed on December 27, 2016, which retrieved 88 records without duplicates. Among these papers, three ultimately met all eligibility criteria. The three studies included a total of 61 individuals, with follow-up ranging from 6 months to 10 years and sample collection from 10 to 24 years. The findings demonstrated that the outcome of surgical removal of lower lip pits was better with the use of vertical wedge excision, inverted-T lip reduction, Mutaf–Goldstein technique and modified simple excision than with simple excision. Simple excision may result in postoperative complications, such as mucocele and pit recurrence.     

干扰素调节因子6基因致病的Van der Woude综合征的家系调查和遗传特点分析

目的 探讨中国人Van der Woude综合征（VWS）的临床表型及遗传学特点。方法 先证者法收集14个VWS家系并进行口腔专科检查、家系调查及基因突变分析,分析不同VWS家系个体或同一家系不同个体的临床表型,绘制家系图谱,明确遗传方式及致病基因,计算表型分布频率和表型基因频率。结果 VWS家系基本符合常染色体显性遗传特征,患者多数表现为典型的VWS,致病基因为干扰素调节因子6（IRF6）。VWS表型分布频率为：唇瘘91.9%,唇腭裂73.0%,牙畸形8.1%。不同家系个体和同一家系的不同个体临床表型存在明显差异。结论 收集的家系均为常染色体显性遗传,表现度变异大。中国人群VWS致病基因为IRF6,为Ⅰ型VWS。     

Novel IRF6 mutations in Chinese patients with Van der Woude syndrome

Van der Woude syndrome (VWS) (OMIM 119300) is a dominantly inherited, developmental disorder that is characterized by pits and/or sinuses of the lower lip and a cleft lip and/or cleft palate. Mutations in the interferon regulatory factor 6 gene (IRF6) have been recently identified in patients with VWS, with more than 60 mutations reported. However, the VWS phenotype, IRF6 mutation genotypes, and their interrelationships in Chinese VWS patients have not been studied. Here, we report 11 Chinese families with variable clinical phenotypes of VWS and identified mutations in all patients. Of the 11 mutations, 8 appeared to be novel: CC5.6GT, T342A, 566delA, C748T, C756A, C989A, C1209G, and 1316delT. Seven mutations caused a change or loss of the IRF6 domain. The marked phenotypic variation may be caused by the action of certain modifier genes on IRF6 function.     

Two missense mutations in the IRF6 gene in two Japanese families with Van der Woude syndrome

Van der Woude syndrome (VWS) is a common autosomal dominant disorder with cleft lip and/or palate and lower lip pits. Its prevalence is estimated to be 1/33,600 in the Finnish Population, and 1/47,813 in the Japanese. We performed mutation analysis of the IRF6 gene by direct sequencing in 2 unrelated Japanese families that consist of a total of 3 affected members with cleft lip and palate associated with lower lip pits. Consequently, we found novel base substitutions, 25C>T, in IRF6-exon 3 in a boy, his mother, and his phenotypically normal maternal grandmother in one of the families. A known mutation, 250C>T, was identified in exon 4 of a girl and her unaffected father in the other family. The same mutations were never observed among 190 healthy Japanese. The results indicate incomplete penetrance and variable expressivity in the families. Because 25C>T and 250C>T predict to lead to R9W and R84C substitutions, respectively, at the most conserved DNA binding domain of IRF6, and because arginine at positions 9 and 84 is highly conserved among IRFs, the 2 mutations may lead to abolish the DNA binding activity in the developing craniofacial region. To our knowledge, this is the first report of IRF6 mutations observed in Japanese VWS patients.