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.     

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。     

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。     

一先天缺牙家系基因芯片检测分析及FGF20基因的检测

目的 研究一先天缺牙家系的遗传学特点并探寻其可能的致病基因。方法 一先天缺牙家系3代共17人,在患者和家属知情同意及伦理委员会批准的前提下对全部成员进行临床检查和X线辅助检查,抽取其家系成员静脉血,提取DNA,应用基因芯片技术进行基因筛查,对可疑基因FGF20进行聚合酶链式反应（PCR）并测序。结果 该非综合征型先天缺牙家系为3代连续遗传,且没有性别差异,外显率为100%,诊断为常染色体显性遗传;基因芯片检测提示FGF20可能为该家族先天缺牙的致病基因,但经PCR检测未发现突变位点。结论 先天缺牙的致病机制较复杂,可能是多基因联合控制的疾病;基因芯片技术在筛查牙齿先天缺失家系的致病基因方面仍有一定的局限性。     

非综合征型先天性牙发育不全的临床研究

目的 探讨非综合征型先天性牙发育不全（NSTA）的临床特点。方法 对已确诊的4个非综合征型先天性牙发育不全先证者所在的家系18名成员（11名患病,7名正常）进行研究。行口腔专科检查、口腔全景片检查和进行家系调查与遗传学系谱分析。取外周静脉血行实验室检查,行染色体分析（常染色体数、性染色体数、核型、数目畸变率、结构畸变率等）,检测血清微量元素铜、锌、铁、镁、钙及血清碱性磷酸酶（ALP）。结果 本组病例各患者牙齿大小、形态和牙列畸形等临床表现各不相同,呈多样性。罹患牙齿的牙位具有选择性,以上下颌侧切牙发病率最高,其次为尖牙,再其次为前磨牙和第二磨牙, 第一磨牙发病率及上颌中切牙最低;本组4个家系调查表现为常染色体显性遗传。血清微量元素及碱性磷酸酶（ALP）检测基本正常。结论 非综合征性先天性牙发育不全其临床表现具有多样性,但罹患牙齿（包括缺失牙和畸形牙）的牙位具有选择性。     

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。     

遗传性牙龈纤维瘤病（附2例报告）

目的通过探讨遗传性牙龈纤维瘤病（HGF）的临床特点及治疗方法,增进对本病的认识,从而提高诊断治疗水平。方法先证者法收集两个HGF家系全部成员资料,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,绘制系谱图,分析可能的遗传方式。对两名先证者采用手术治疗。结果两家系发病患者均符合非综合征型HGF特征。发病患者不同个体间的表现度不同。两家系均符合常染色体显性遗传特征。经随访,手术患者治疗效果良好。结论 HGF遗传方式以常染色体显性遗传为主,且同一家系的不同受累个体其增生程度轻重不一,极具差异,具有高度遗传异质性。手术是治疗该病的有效的方法。     

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。     

非综合征型先天缺牙的研究进展

先天缺牙是人类牙列中最常见的发育异常，多为恒牙缺失，乳牙先天性缺失少见。可见为散发病例或家族遗传形式，后者可以是常染色体显性遗传、常染色体隐性遗传或X染色体遗传。先天缺牙根据是否有伴发症状，可分为：①单纯性或非综合征型先天缺牙，即仅有牙齿的先天缺失；②综合征型先天缺牙，即先天缺牙同时伴有其他器官的发育异常。根据缺牙数目可分为个别牙缺失、多数牙缺失和先天性无牙。多数牙缺失是指缺牙数目在6个及6个以上者（不包括第三磨牙）。     

一个遗传性釉质发育不全家系的临床及致病基因研究

目的:探讨一个遗传性釉质发育不全(amelogenesis imperfecta, AI)家系的临床表型和致病基因,为该病的临床诊断和遗传咨询提供依据。方法:收集先证者及其家系成员的临床资料,同时采集家系成员的外周血,提取全基因组DNA,全外显子组测序检测可能的致病基因,进一步对候选变异进行Sanger测序验证。结果:该家系患病成员的临床表现为全口牙呈黄褐色,釉质质地较软,剥脱磨损,牙面粗糙不规则,釉质密度接近牙本质,符合AI中的亚型钙化不全型的临床表型;同时该家系患病成员在FAM83H基因第5外显子上均存在c.1366C>T(p.Gln456~*)的无义突变,已有该变异致病性的相关报道,且未患病的家系成员未发现上述突变。结论:该家系患有常染色体显性遗传钙化不全型AI,FAM83H基因第5外显子c.1366C>T(p.Gln456~*)的无义突变是该家系的致病原因,本研究为该家系的诊断和遗传咨询提供依据。     

一个中国汉族先天性附耳表型致病基因的定位研究

目的定位一个中国汉族先天性面部畸形家系附耳表型的致病基因。方法通过全基因组扫描、连锁分析和单体型分析用微卫星遗传标记在染色体区域定位致病基因。结果全基因组扫描和连锁分析发现,附耳的致病基因可能定位于d18s462～d18s70之间,遗传距离为6.00cM,LODZMAX=1.83（d18s462,θ=0.06）;或者d7s2546～d7s559之间,遗传距离为8.94cM,LODZMAX=2.74（d7s2546,θ=0.05）。再经过单体型分析将其致病基因定位在d7s2546～d7s550之间,遗传距离为5.38cM。结论这个中国汉族家系附耳表型的致病基因定位d7s2546～d7s550之间,在染色体的位置为7q36.1～q36.2。     

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.     

Exclusion of candidate genes in two families with autosomal dominant hypocalcified amelogenesis imperfecta

The amelogenesis imperfectas (AI) are a group of hereditary enamel defects characterized by clinical and genetic diversity. The most common AI types are inherited as autosomal traits. Three mutations of the enamelin (ENAM) gene have been found in cases of autosomal dominant hypoplastic AI. The gene(s) responsible for hypocalcified forms of AI have not been identified, although a number of autosomal genes have been proposed as candidates for AI based on their expression by ameloblasts, including ameloblastin and enamelin (chromosome 4q13.3), tuftelin (chromosome 1q21), enamelysin (chromosome 11q22.3-q23) and kallikrein 4 (chromosome 19q13.3-q13.4). To localize the gene(s) responsible for autosomal dominant hypocalcified AI, we evaluated support for/against linkage of AI to genetic markers spanning five AI candidate genes in two extended families. Our data excluded all proposed candidate gene regions as causal for autosomal dominant hypocalcified AI in these families. These linkage findings provide further evidence for genetic heterogeneity among families with autosomal dominant AI and indicate that, at least, some forms of autosomal dominant hypocalcified AI are not caused by a gene in the five most commonly reported AI candidate genes.     

遗传性乳光牙本质的固定修复1例

遗传性牙本质发育不全是一种临床较少见的常染色体显性遗传病。本文报告1例遗传性乳光牙本质病例,并结合相关文献,就其临床表现及治疗进行讨论。     

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.     

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.     

家族性巨大型牙骨质瘤家系致病基因新发突变和临床表型分析

目的: 应用全外显子测序技术对家族性巨大型牙骨质瘤（familial gigantiform cementoma, FGC）家系进行测序,筛选致病基因及突变,并探讨基因型与临床表型的关系。方法: 纳入以颌骨畸形、下肢长骨骨折为主要表现的1个FGC家系9例患者, 评估患者临床表现、骨影像学、骨密度、骨转换相关生化等指标。提取9例患者及家系中14名未患病者外周血基因组DNA,进行全基因组外显子捕获及高通量测序,通过生物信息学分析、确定突变位点,利用Sanger测序法对384名未患FGC且无此疾病家族史的受试者进行验证。结果: FGC主要表型为上、下颌骨 4 个象限内均存在弥漫性多发病灶,以下颌骨体前部尤为严重,颌骨畸形明显;并伴有全身骨密度下降,常因轻微外力导致多次下肢长骨骨折。全外显子测序发现,所有患者均存在ANO5（c.1538C> T, p.Thr513Ile）杂合突变,该突变影响ANO5蛋白功能与结构。结论: FGC是罕见的常染色体显性遗传疾病,中国FGC患者以颌骨畸形、下肢长骨骨折、骨密度降低为主要表型。ANO5基因突变是目前唯一致病基因, 扩展了对FGC表型和致病基因突变型的认识。     

Further evidence of genetic heterogeneity segregating with hereditary gingival fibromatosis

Aim: To clinically characterize and map the disease-associated locus in a five-generation Chinese family with autosomal dominant early-onset hereditary gingival fibromatosis (HGF).
Material and Methods: A complete oral examination was conducted. Genomic DNA samples were obtained from 14 individuals. Short tandem repeats markers, which encompass four previously known loci related to HGF, were genotyped. Two-point log of the odds (LOD) scores were calculated using MLINK program of the LINKAGE software, multipoint and non-parametric linkage (NPL) analysis were performed using the GENEHUNTER software.
Results: Clinical evaluation and histological examination of this family suggested typical features of HGF. The onset age was early in the generations, ranging between 1 and 2 years. None of the tested markers showed cosegregation among affected individuals. Genotyping data from four putative regions yielded significant negative two-point LOD scores (<−2.0) at θ=0. The maximum multipoint LOD scores and NPL analysis revealed exclusion of these loci as well.
Conclusions: Exclusion of linkage in this family to any of the known HGF loci proved the existence of a novel locus for autosomal dominant HGF and showed that this rare disorder is far more heterogeneous than previously expected.     

遗传性釉质发育不全家系致病基因的定位研究

目的定位遗传性釉质发育不全（AI）家系的致病基因。方法收集1个常染色体显性AI家系,提取该家系19名成员（其中患者9例）的外周血DNA,选择横跨釉蛋白基因、成釉蛋白基因、釉丛蛋白基因、基质金属蛋白酶基因、丝氨酸蛋白酶基因5个候选基因的短串联重复序列（STR）,进行PCR扩增,经变性聚丙烯酰胺凝胶电泳确定基因型,并进行连锁分析。结果得到19名个体的8个STR位点的基因型,分别为D1s498、D1s2343、D4s1543、D4s2361、D4s2969、D11s1339、mmp20、D19s246。连锁分析结果显示各位点的LOD值在重组率为0时均小于1,不支持该家系的致病基因与5个侯选基因上的STR位点的连锁关系。结论连锁分析结果不支持该家系致病基因定位于已知基因座处,提示至少某些常染色体显性AI家系的致病基因不是文献所报道的AI候选基因,进一步证实了常染色体显性遗传性釉质发育不全的遗传异质性。