常染色体显性遗传性牙龈纤维瘤病的临床和遗传学特点分析

目的：探讨遗传性牙龈纤维瘤病(HGF)的临床表型和遗传学特点。方法：先证者法收集5个HGF家系并进行问卷和口腔检查，观察不同家系及同一家系不同个体的临床表型和发病特点，分析可能的遗传方式，绘制系谱图。结果：所有家系符合常染色体显性非综合征型HGF特征，发病年龄在牙齿萌出期，患者均有典型的牙龈增生，但不同个体其增生范围和严重程度有明显差异。龈切术可极大地恢复口腔功能和颜面外形，但部分病例在术后有复发倾向。结论：收集的5个家系均为非综合征型常染色体显性遗传HGF，且疾病外显率高，表现度变异大。     

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。     

牙本质发育异常家系调查和表型分析

目的:调查和分析中国人牙本质发育异常家系及临床表型,进一步明确其诊断和分型。方法:采用先证者查证法调查和收集中国人牙本质发育异常家系,绘制系谱图,确定遗传方式,根据临床表现和X线征象特点对各家系受累个体进行表型分析。结果:共收集4个中国人牙本质发育异常家系,家系Ⅰ、Ⅱ、Ⅲ为常染色体显性遗传的Ⅱ型牙本质发育不全,家系Ⅳ先证者符合Ⅱ型牙本质发育不全诊断;临床表型在各家系及同一家系不同个体间存在异同。结论:独立发生于牙本质的各型遗传性牙本质发育异常存在共有表型,可作为同一类疾病研究。     

家族性巨颌症二家系临床病理分析

目的 探讨家族性巨颌症的遗传学及临床病理学特征。方法调查两个巨颌症家系，确定家系发病的树状图。对巨颌症患者进行临床资料及X线征象分析、组织学观察并随访。结果两个巨颌症家系均连续3代发病，家系A受累个体现存活2人，家系B受累3人，两个家系的先证者均诊断为巨颌症Ⅳ级，组织学上可见典型的多核巨细胞及嗜伊红血管套，部分病变活跃区可见明显的核分裂象，病变相对静止区可见疏松纤维组织和骨组织。结论经家系分析，巨颌症符合常染色体显性遗传规律，临床需要根据患者的家族史、临床表现、X线征象及组织病理学特点进行诊断。     

一个非综合征型多数牙缺失家系的临床及遗传学特征分析

目的:探讨一个非综合征型多数牙缺失家系的临床表型及遗传学特点.方法:对家系内部分患者及正常成员进行口腔专科检查和家系调查,总结分析其临床特征,并绘制系谱图以明确其遗传方式.结果:(1)该家系符合常染色体显性遗传模式,外显率较高;(2)患者牙列发育异常表现在牙齿数目、形态、位置及(牙合)关系等方面,先天缺牙以第二前磨牙及第三磨牙较为常见;(3)家系内不同个体的临床表型存在差异. 结论:该家系中,先天性缺牙呈常染色体显性遗传模式,外显率较高,表型差异较大.其临床特征以第二前磨牙和第三磨牙先天缺失较为多见.     

先天性舌系带过短畸形一家系报告

先证者 :男 ,36岁 ,发卷舌音障碍 ,舌系带附丽向舌尖部明显前移 ,卷舌受限。染色体检查中未发现异常。调查该家系三代 9人 ,患者 4例 (患者畸形程度相近 ) ,其中男 2例 ,女2例。　　作者单位 :163 712黑龙江省大庆市第四医院口腔科　　该家系有常染色体显性遗传特点 ,先证者女儿、妹妹及父亲皆出现程度相近畸形。双亲之一是患者 ,子女可发病 ;双亲无病 ,子女无患者 (除非基因突变 )。连续三代发病 ,患病比率为 4 / 9。男女机会均等。附图　 1例舌系带过短畸形系谱先天性舌系带过短畸形一家系报告@曹国绩!163712$黑龙江省大庆市第四医院口腔…     

外胚叶发育不全一家系的基因型分析

目的:分析外胚叶发育不全家系的表型特点和遗传特征,并对家系基因型进行分析。方法:收集1个外胚叶发育不全家系,采用临床检查和家系调查的方法,调查并记录先证者及家系成员的病史和体格检查资料。对家系成员EDAR基因开放阅读框内外显子编码区及外显子-内含子接头区核苷酸序列进行分析。结果:收集到的家系为常染色体显性遗传,患者临床表现典型,家系内表现度差异小。家系成员EDAR基因开放阅读框内未检测到基因突变。结论:本研究收集的外胚叶发育不全家系临床症状明显,致病基因排除EDAR基因。     

遗传性牙龈纤维瘤病家系永生化细胞库的建立及染色体初步分析

目的:建立遗传性牙龈纤维瘤病(HGF)家系外周血永生化淋巴细胞系,以永久保存现有患病家系特有的基因组资源,并探讨将其作为HGF发病机理研究的生物材料的可行性和可靠性.方法:在知情同意原则下,收集5个常染色体显性遗传HGF家系外周血样品,采用新鲜血法和冻存白细胞法,通过EB病毒(EBV)联合环孢霉素A(CyA)转化处理获得外周血永生化淋巴母细胞系,制备并分析细胞系的中期染色体片,检测建系前后的遗传稳定性.结果:成功建立5个HGF家系的永生化B淋巴母细胞系,所有建成细胞系冻存后复苏成功率达100%,转化前后的淋巴母细胞系G带显色核型分析无明显差异.结论:EB病毒转化构建的永生化淋巴细胞系遗传学特性稳定,可永久保存HGF家系资源,为今后在细胞和分子水平上开展HGF发病机理、诊断和治疗提供随时可取的实验材料奠定了基础.     

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。     

中国汉族人群侵袭性牙周炎遗传方式初探

目的 初步探讨中国汉族人群侵袭性牙周炎( aggressive periodontitis,AgP)可能的遗传方式.方法 采用医学遗传数理统计方法中的分离分析方法(先验法+理论子女总数校正法)及多基因遗传的Edwards法对73个中国汉族人群AgP家系资料进行遗传方式分析.结果 AgP同胞患病率与一般人群AgP患病率的比值接近1/√q(q为人群患病率),符合多基因遗传;先验法结果显示将所有家系作为一个整体进行分析符合常染色体隐性遗传,理论子女总数校正后的分离率为0.2419,分离比接近常染色体隐性遗传模式的理想分离率0.25;x2测验法的结果同时显示亲代为重度牙周炎患者的家系有常染色体显性遗传的可能性.结论 本组中国汉族人AgP在遗传方式上存在异质性,常染色体隐性遗传方式占优势,但是亲代为重度慢性牙周炎患者的家系存在常染色体显性遗传的可能,提示AgP可能是存在着主效基因控制的复杂性疾病.     

遗传性牙龈纤维瘤病的临床研究

目的探讨遗传性牙龈纤维瘤病(hereditary gingival fibromatosis,HGF)的临床特征。方法回顾分析我院2001-2007年收治的3例HGF病例,对其遗传特点及相关的综合征,临床表现,X线片特征,组织病理,诊断分型及治疗预后进行分析。结果3例HGF患者1例为综合征型HGF,2例为非综合征型HGF,其遗传特性、发病年龄、临床表征各有所不同,但均具有典型全口牙龈增生及牙槽骨吸收。结论3例HGF不同个体表现不尽相同,具有一定的异质性。     

Hereditary gingival fibromatosis: a systematic review

Generalized gingival enlargement can be caused by a variety of etiological factors. It can be inherited (hereditary gingival fibromatosis [HGF]); associated with other diseases characterizing a syndrome; or induced as a side effect of systemic drugs, such as phenytoin, cyclosporin, or nifedipine. HGF, previously known as elephantiasis gingivae, hereditary gingival hyperplasia, and hypertrophic gingiva, is a genetic disorder characterized by a progressive enlargement of the gingiva. This review will focus on diagnosis, treatment, and control of HGF. The pattern of inheritance, the histopathologic characteristics, and the known biologic and genetic features associated with HGF are also emphasized.     

Ultrastructural aspects of connective tissue in hereditary gingival fibromatosis.

OBJECTIVE: The purpose of this study was to analyze the ultrastructure of gingival connective tissue from patients in one family affected by hereditary gingival fibromatosis (HGF). STUDY DESIGN: Electron microscopic examination was performed with gingival tissue from 10 patients from a Brazilian family with 132 members. Fifty of 96 persons at risk for this disorder were affected, which is consistent with an autosomal dominant pattern of inheritance. RESULTS: The extracellular matrix showed flocculent material and collagen fibrils with structural abnormalities and variation in diameter. Increased numbers of oxytalan fibers were identified; however, elastic fibers were rare in the analyzed areas. CONCLUSIONS: The structural alterations found in HGF appear similar to those described in certain other heritable collagen disorders, suggesting that HGF should be included in the group of hereditary diseases in which connective tissue alterations have a distinct pattern, in contrast to reactive fibrotic gingival enlargements with no genetic component.     

Hereditary gingival fibromatosis--a review

Hereditary gingival fibromatosis (HGF) is a rare gingival lesion that presents as localized or generalized enlargement of the attached gingiva. The gingiva is characterized as pink, firm, and very fibrous, with little tendency to bleed. HGF can present as an isolated feature or as part of a syndrome. Recent findings report a defect in the Son of sevenless-1 gene on chromosome 2p21-p22 (HGF1) as a possible cause of this clinical presentation. HGF inheritance is transmitted through both autosomal dominant and recessive modes. While clinicians disagree on the modalities and timing of treatment for HGF, the clinical condition generally requires repeated resective periodontal surgical procedures over the patient's lifetime. This article reviews differential diagnosis, etiology, complications, and treatment of HGF.     

Hereditary gingival fibromatosis: report of a five-generation family using cellular proliferation analysis

BACKGROUND: Hereditary gingival fibromatosis (HGF) is an uncommon condition characterized by an accumulation of extracellular matrix resulting in a fibrotic enlargement of the gingiva. The goal of this article is to describe one kindred affected with HGF and discuss the diagnosis, treatment, and control of the disease. The pattern of inheritance, histopathologic characteristics, and proliferative potential of epithelial and mesenchymal cells of HGF are also emphasized. METHODS: To characterize the pattern of inheritance and the clinical appearance of gingival overgrowth, 117 family members were examined. The recurrence risk was estimated by the use of a genetic analysis program. Immunohistochemistry against the proliferating cell nuclear antigen (PCNA) and pKi-67 was performed to assess cellular proliferation of normal gingiva (NG) and HGF cells. RESULTS: Examination of the family pedigree demonstrated an autosomal dominant trait of inheritance, and a sibling recurrence risk of 0.085 and an offspring recurrence risk of 0.078, indicating that HGF was a consequence of genetic alteration with low penetrance. Unaffected and affected members transmitted the disease to their offspring. The affected patients showed a generalized but mild gingival overgrowth. Surgical treatment consisted of a combination of gingivectomy and gingivoplasty. Histologic examination showed that the gingival lesions of all patients were quite similar, with increased amounts of collagen fiber bundles in the connective tissue. Immunohistochemistry revealed that the proliferative potential of epithelial cells was significantly higher in the HGF group compared to the NG group, whereas mesenchymal cells from both groups were negative for the proliferative markers. CONCLUSION: Our data demonstrated that, in the studied family, HGF is transmitted by an autosomal dominant pattern with incomplete disease penetrance, and although the gingival enlargement resulted from an excessive accumulation of collagen fibers, HGF is characterized by an increase in the proliferation rate of epithelial cells.     

Hereditary gingival fibromatosis: Clinical and ultrastructural features of a new family

Objective: This article describes the diagnosis, clinical and microscopic (histopathology and ultrastructural) features and treatment of a new family with hereditary gingival fibromatosis (HGF) and highlights the importance of this genetic condition. Study Design: To characterize the pattern of inheritance and the clinical features, members of a new family with HGF were examined. The pedigree was reliably constructed including the four latest generations of family. Hematoxylin and eosin staining and ultrastructural analysis were performed with the gingival tissue. Results: Examination of the family pedigree revealed that the patient III-2 represent the index patient of this family (initial patient with a mutation), which was transmitted to her daughter through an autosomal dominant mode of inheritance. The affected patients showed a generalized gingival overgrowth. The patient was treated with surgical procedures of gingivectomy and gingivoplasty. The diagnosis was confirmed by histopathology examination that showed a well-structured epithelium with elongated and thin papillae inserted in fibrous connective tissue with increased amount of collagen. The ultrastructural aspects of the tissue show collagen fibrils exhibiting their typically repeating banding pattern with some fibrils displaying loops at their end. Moreover, it was possible to seen in some regions fibrillar component presenting tortuous aspects and loss of the alignment among them. Conclusions: This HGF frequently resulted in both esthetic and functional problems. The genetic pattern of this Brazilian family suggested a new mutation, which was later transmitted by an autosomal dominant trait. Key words:Gingival fibromatosis, genetic disease, pedigree, ultrastructure.     

Evidence of genetic heterogeneity for hereditary gingival fibromatosis

Hereditary Gingival Fibromatosis (HGF) is the most common genetic form of gingival fibromatosis. The condition is most frequently reported to be transmitted as an autosomal-dominant trait, but autosomal-recessive inheritance has also been reported. The clinical presentation of HGF is variable, both in the distribution (number of teeth involved) and in the degree (severity) of expression. It is unknown if the variable clinical expression of HGF in different families is due to variable expression of a common gene mutation, allelic mutations, or non-allelic mutations. The apparently different modes of Mendelian inheritance of HGF suggest genetic heterogeneity. A gene locus for HGF has been localized to a 37-cM genetic interval on chromosome 2p21-p22 (D2S1352, Zmax = 5.10, theta = 0.00) flanked by D2S1788 and D2S441. To evaluate the generality of this linkage, we tested linkage with 9 markers from this candidate region in another large family, segregating for an autosomal-dominant form of generalized HGF, and found no support for linkage with any of these markers. Furthermore, statistical tests of this apparent heterogeneity were highly significant. Analysis of these data provides direct evidence that at least two genetically distinct loci are responsible for autosomal-dominant hereditary gingival fibromatosis.     

Nonsyndromic hereditary gingival fibromatosis: Characterization of a family and review of genetic etiology

Our aim is to describe a family with a nonsyndromic form of hereditary gingival fibromatosis (HGF) and discuss genetic characteristics of this rare disease by reviewing reported cases. A mother and three descendants were diagnosed with HGF. There was marked variable expressivity: from severe generalized gingival overgrowth in a 16-year-old boy (the proband) to minimal manifestations in the mother. The proband was submitted to gingivectomy and gingivoplasty. In younger siblings, the disease remained stable for 5 years, suggesting that clinical surveillance is a good option. The diagnosis was supported by histopathological examination. Analysis of this family and literature-reported cases supports that HGF most frequently shows an autosomal dominant inheritance with high penetrance and variable expressivity. Neomutations and gonadal mosaicism do not seem to be a rare event. Although five loci have been mapped by linkage analysis, only two genes, SOS1 and REST, were identified in four families.