A POTENTIAL TUMOR SUPPRESSOR GENE: Doc-1R

Objective: To detect the expression and the genomic sequence of Doc-1R gene in mice. Methods: The gene specific primers were designed and synthesized according to the cDNA sequence of Doc-1R gene. The sequence of Doc-1R gene was cloned by nested PCR. The expression of Doc-1R gene was examined by RT-PCR in thirteen kinds of tissues of mice. Results: The mouse Doc-1R gene has been obtained by two times genomic walking, which spans 2787 bp and contains four exons and three introns. All of the splice donor/acceptor site sequences are in accordance with the consensus 揋T-AG?rule. There was expression of Doc-1R gene in the thirteen tissues. Conclusion: The mouse Doc-1R gene was cloned successfully. The expression pattern suggests that Doc-1R gene is a housekeeping gene, which is important to keep the function of tissues and organs.

小鼠Doc-1R基因的克隆及其表达

背景与目的:Doc-1R基因是1999年克隆的一种新的基因,已有的研究表明Doc-1R基因可能是一种潜在的抑癌基因。为了进一步研究此基因的功能,我们首先克隆了小鼠的Doc-1R基因,并对此基因的表达进行了初步的研究。方法:根据小鼠的Doc-1R基因cDNA序列,设计合成基因组特异引物,应用巢式PCR对小鼠基因组步移文库进行扩增。对测序结果进行序列分析及剪接位点的鉴定。另外应用RT-PCR的方法研究了Doc-1R基因在小鼠肝、脾、胰、肾、肺、肠、心、脑、骨、肌肉、膀胱、卵巢、睾丸等13种组织的表达。结果:经二次基因组步移获得了小鼠Doc-1R基因组全长序列。基因组全长2787bp,含4个外显子和3个内含子,外显子与内含子接头符合GT/AG法则。RT-PCR结果表明,Doc-1R基因在小鼠13种组织和器官中均有表达。结论:成功克隆了小鼠Doc-1R基因,为进一步研究此基因的功能奠定了基础。RT-PCR表达结果提示此基因可能是对维持组织器官的功能具有重要的作用的管家基因。

Variations of Melanocortin Receptor 1 (MC1R) Gene in Three Pig Breeds

Variations of Melanocortin Receptor 1 （MC1R） were investigated using sequencing, PCR-RFLP and PCR-SSCP, in three pig breeds, Landrace, Yorkshire, and Duroc. Five polymorphic sites were found, in which 668G→C occurred within 5＇ UTR, nt894insCC in coding region resulting in a premature stop at codon 56, and 1318C→T, 1554G→A, l197G→A in coding region resulting in Ala164Val, Ala243Thr, and Asp124Asn respectively. All individuals in Landrace and Yorkshire present homozygous 668GG, 1197AA, 1318CC, and 1554GG, and have CC insertions at the 894 site, whereas the individuals in Duroc present a contrast homozygous 668CC, 1197GG, 1318TT, and 1554AA, and have no CC insertions at the corresponding site. No heterozygote has been found at these mutation sites. Presumably, 668G→C, 1318C→T, and 1554G→A may be associated with the recessive red color in the Duroc breed, and nt894insCC making 1197G→A nonsense may be associated with the white color in Landrace and Yorkshire breeds.

小鼠DOC-1R反义重组载体的构建及表达的研究

背景与目的:DOC-1R(deletedinoralcancer-1related)基因是一个候选的抑癌基因,它与CDK2特异性结合后,抑制CDK2与cyclin形成复合物,进而对细胞周期进行调控。本研究拟构建DOC-1R反义重组质粒,并研究该基因表达受到抑制后对正常细胞增殖产生的影响。方法:小鼠DOC-1R基因筛选后构建pcDNA3-DOC-1R反义重组质粒,经细胞转染,通过细胞增殖能力测定、软琼脂培养观察DOC-1R对细胞生长状态的影响。结果:小鼠DOC-1R基因转染的NIH3T3细胞较空载体转染的细胞生长速度有较明显的差异。正义重组体pcDNA3-DOC-1R+可明显抑制细胞增殖,而反义重组体pcDNA3-DOC-1R-则促进细胞的增殖。在软琼脂培养中,正义重组体在软琼脂培养基中成集落能力下降,一方面克隆形成率下降,另一方面形成的集落也普遍较小;而反义重组体明显增加了成集落能力,克隆形成率也较正义重组体有明显的增加。结论:小鼠DOC-1R基因可明显抑制细胞的生长速度和成集落能力,这一作用有助于进行正常细胞生长、增殖规律和肿瘤治疗、预防方面的研究。

人口腔癌症缺失相关蛋白(DOC-1R)的表达、纯化和晶体生长

口腔癌缺失(DeletedinOralCancer-1,DOC-1)基因是近年来被证实的口腔癌中具有抑癌作用的基因。1999年,研究人员通过酵母双杂交实验又发现了与DOC-1相关的另一候选抑癌基因DOC-1R(DOC-1related)。以往的很多实验表明,这两个蛋白无论序列还是功能上都非常相似。然而,其三维结构以及与其他重要蛋白相互作用的机制一直还不清楚,PDB库中也未见其相关同源结构的报道。作者将人DOC-1R基因的cDNA片段克隆至原核表达载体pET-22b(+)中,通过IPTG诱导获得高效表达,再经过Ni-NTA亲和层析和Superdex75层析柱纯化,获得了纯度达到96%以上的蛋白。质谱分子量测定显示DOC-1R的分子量为14091.23Da,与理论分子量基本一致;动态光散射实验显示蛋白均一性高达99.0%,可用于晶体生长;采用悬滴气相扩散法筛选,在多个条件下得到了DOC-1R的微晶。为DOC-1R的三维结构解析奠定了坚实的基础。

Melanocortin-1 receptor gene variants in four Chinese ethnic populations

There is strong relationship between melanocortin-1 receptor (MCIR) gene variants and human hair color and skin type. Based on a sequencing study of MC1R gene in 50 individuals from the Uygur, Tibetan, Wa and Dai ethnic populations, we discuss the occurrence of 7 mc1r variants consisting of 5 nonsynonymous sites (Val60Leu, Arg67Gln, Val92Met, Arg163Gln and Ala299Val) and 2 synonymous sites (C414T and A942G), among which C414T and Ala299Val were reported for the first time. Confirmation and analysis were the made of 122 individuals at three common point mutations (Val92Met, Arg163Gln, A942G) using PCR-SSCP. The frequency of Arg163Gln variant varies in the four ethnic populations, with percentage of 40%, 85.0%, 66. 2% and 72.7%, respectively, while those of Val92Met and A942G are roughly similar in these four populations. The different environments, migration and admixture of various ethnic groups in China might have impact on the observed frequency of Arg163Gln.

Polymorphisms in CYP2R1 Gene Associated with Serum Vitamin D Levels and Status in a Chinese Rural Population

Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D] and it is a useful clinical biomarker of vitamin D status. The Institute of Medicine (IOM) defines as vitamin D deficiency (VDD) when serum 25(OH)D concentration is less than 20 ng/mL⑴.Worldwide, VDD is recognized as a severe public health problem. In 2007, Holick estimated that globally over one billion people suffered from VDD or vitamin D insufficiency (VDI). In China, it has bee n reported that the prevale nee of VDD ranged from 38.8% to 91.2% in different regions.

PDRG1 at the interface between intermediary metabolism and oncogenesis

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

Cloning and Expression Level Analysis of Melanocyte-stimulating Hormone Receptor 1 Gene(MC1R) in Alpacas with Different Coat Color

Specific primers for the MC1R gene of alpacas(GenBank EU1358800) were designed to amplify the cDNA sequence using RT-PCR to seek variation in the sequence and explore the relationship between the expression level of MC1R gene and alpaca coat color.The MC1R gene from white alpaca was cloned successfully and sequence analysis verified that the MC1R gene,encoding 317 amino acids,was 1081 bp in length.Compared with the existing sequence in GenBank,sequence identity was 99.9%and 7 mutations were found.Primers,designed from the sequence obtained,were used to assess the relative expression of MC1R in alpacas of different coat color using QRT-PCR and SPSS 13.0 software.Relative expression of MC1R in the skin of brown alpacas was 4.32 times higher than that in white alpacas after normalization with GAPDH(P【0.01),indicating that MC1R expression may be related to coat color of alpacas.

Relationship between R219K polymorphism of adenosine triphosphate-binding cassette transporter 1 gene and cerebral infarction: A case-controlled analysis

BACKGROUND： Studies have shown that adenosine triphosphate-binding cassette transporter 1 （ABCA1） gene influences atherosclerosis. Studies have also demonstrated that cerebral infarction does not occur often in pre-menopausal women. It has been, therefore, assumed that sex plays a role in R219K polymorphism of ABCA1 gene and cerebral infarction. OBJECTIVE： To explore the relationship between lipid metabolism-correlated R219K polymorphism of ABCA1 gene, risk factors of cerebral infarction and lipid level, and to determine whether there were significant differences in gender between R219K polymorphism of ABCA1 gene and cerebral infarction. DESIGN, TIME AND SETTING： A multicentral and non-randomized, controlled study based on gene polymorphism was performed at the Chinese National Human Genome Center, and lipid concentrations were measured at Beijing Xuanwu Hospital. Patients with cerebral infarction and healthy subjects were enrolled from eight hospitals of six provinces of China between October 2002 and December 2004. PARTICIPANTS： There were 177 patients in the cerebral infarction group, including 119 males and 58 females, with a mean age of （60 -＋ 13） years, and 234 healthy subjects in the normal control group, including 79 males and 155 females, with a mean age of （58 ± 12） years. METHODS： R219K polymorphism of the ABCA1 gene was detected using polymerase chain reaction-restriction fragment length polymorphism, and blood lipid concentrations were simultaneously measured. MAIN OUTCOME MEASURES： Genotype and allele frequency of R219K polymorphic site, and blood lipid concentrations. RESULTS： RR genotype and R allele frequency of males in the cerebral infarction were significantly greater than males in the normal control group [RR genotype： x2 = 5.305, OR （95% CO, 2.326 （1.120 4.828）, P〈 0.05; R allele： x2= 4.219, OR （95% CO, 1.528 （1.019 2.292）, P〈 0.05]. In addition, RR genotype and R allele frequency of males were significantly greater than females in the cerebral infarction group [RR genotype： x2= 5.172, OR （95% C/）, 2.604 （1.120-6.057）, P〈 0.05; R allele： x2= 4.818, OR （95% CO, 1.652 （1.053 2.589）, P〈 0.05]. There were no significant differences between genotype and lipid concentrations between the two groups （P〉 0.05）. CONCLUSION： The RR genotype of ABCA1 R219K might be associated with onset of cerebral infarction in males, but blood lipid concentrations do not relate to R219K polymorphism.

Polymorphism of Coding Sequences of IGF1R Gene in Baise Horses and Thoroughbred

[ Objective]The aim was to study polymorphism of mat-peptide sequence of IGF1 R gene in Baise horses and thoroughbred, which would af- ford reference for the further studies on the dwarf mechanism and molecular breeding in horses. [Method] A total of 57 blood samples of each breed were collected and genomic DNA was extracted by the standard phenol -chloroform method. Five DNA pools of each breed were constituted and polymorphism sites were identified by sequencing PCR products. Frequencies of genotypes and alleles at these sites of each breed were checked by PCR-RFLP. [Result] Four polymorphism sites were identified in exon 2, 5 and 16, including mutations of T406C, T179 627C, G212 077A and G2.12 110A. No difference was found in the frequency of T179 627C between the Baise horses and thoroughbred. The mutation （3212 077A was only found in the thorou- ghbred, and the mutations, T406C and G212 110A, were only checked out in the Baise horses. [ Conclusion] Whether these mutations are associated with horse growth needs further studies.

Cloning and Expression Analysis of <i>TTG</i>1 Gene Related to <i>Rosa rugosa</i>Trichomes Formation

The TTG1 transcription factor plays an important role in the formation of plant trichomes. Based on the R. rugosa transcriptome data, this study cloned a R. rugosa TTG1 gene, named RrTTG1, and carried out bioinformatics analysis and fluorescence quantitative analysis to explore the relationship between TTG1 gene and R. rugosa trichomes formation, in order to lay a good foundation to cultivate a thornless plant in the family Rosaceae. In this experiment, six hybrid cultivars of R. rugosa “Zizhi”, R. rugosa “Xizi”, R. rugosa “Tang fen”, R. rugosa “Hun chun”, R. rugosa “Zi long wo chi” and R. rugosa “Tian e huang” were used as experimental materials, and the cDNA full length of this gene was obtained by RT-PCR and RACE, and the full length of the cDNA was 1348 bp. After bioinformatics analysis, it is predicted that its molecular formula is C1723H2661N465O529S12, the molecular weight is 38.71 KB, and the isoelectric point is 5.00. Its instability index is 54.30, which belongs to unstable protein;and its hydrophilic amino acid distribution is relatively uniform, and the amount is larger than hydrophobic amino acid, which belongs to hydrophilic protein. Phylogenetic tree was constructed for the TTG1 gene. Evolutionary analysis indicated that RrTTG1 is closely related to the TTG1 protein of Rosaceae family, and has a close relationship with other families. The expression analysis showed that the expression of RrTTG1 protein was negatively correlated with the trichome content of R. rugosa stems and leaves. The expression levels of the three spiny varieties of R. rugosa “Hun chun”, R. rugosa “Xizi” and R. rugosa “Zi long wo chi” were lower, and the expressions of the three less thorn varieties of R. rugosa “Zizhi”, R. rugosa “Tian e huang” and R. rugosa “Tang fen” were higher. According to the above results, it was speculated that RrTTG1 is involved in the synthesis of R. rugosa trichomes and belongs to the negative regulation mechanism.

蒙药童格勒格-1四种粗提物对大鼠肝细胞BRL株低密度脂蛋白受体基因表达的影响

目的观察蒙药童格勒格-1(TGLG-1)四种粗提物对大鼠正常肝细胞BRL株低密度脂蛋白受体(LDL-R)基因表达的影响。方法制备出蒙药童格勒格-1的乙醇、正丁醇、乙酸乙酯、石油醚的提取物。体外培养大鼠正常肝细胞BRL株,通过MTT比色法观察蒙药童格勒格-1提取物对大鼠肝细胞体外毒性的量效关系,确定合适的用药浓度。将大鼠肝细胞分为5组,一组为对照组,其余四组为给药组。将四种粗提物以一定的给药浓度与正常大鼠肝细胞培养24 h后,用RT-PCR法测定大鼠肝细胞低密度脂蛋白受体mRNA表达水平。结果蒙药童格勒格-1提取物中正丁醇和乙酸乙酯提取物作用后的大鼠正常肝细胞低密度脂蛋白受体mRNA相对含量高于对照组,具有显著性差异(P<0.01)。乙醇和石油醚提取物与对照组相比,无显著性差异(P>0.05)。结论蒙药童格勒格-1正丁醇和乙酸乙酯提取物能明显增强大鼠正常肝细胞低密度脂蛋白受体基因表达,从而加快血中低密度脂蛋白的清除,起到调控血脂水平的作用。

四个牦牛品种MC1R基因部分序列的多态性研究

为探索4个牦牛品种MC1R基因多态性的相关信息,选取甘南牦牛、天祝白牦牛、青海高原牦牛、大通牦牛4个品种共408头个体为研究对象,采用PCR-SSCP方法分析牦牛MC1R基因部分序列的基因多态性。结果表明,与GenBank中牛MCIR基因序列(登录号:AF445641.1)比对发现,该扩增片段在3 891 bp处发生C→G的突变,在3 912 bp处发生T→C的突变,共发现CC、DD、EE、CD、CE和DE 6种基因型。4个牦牛品种中CD、CE和DE 3种基因型在青海高原牦牛和大通牦牛中占主要优势,这3种基因型频率总和在青海高原牦牛和大通牦牛群体中分别是0.778和0.781。DD和CD两基因型是甘南牦牛群里中的优势基因型,其基因型频率分别是0.351和0.328。天祝白牦牛中优势基因型是DD,其基因型频率是0.500。D等位基因是4个地方品种牦牛中的优势等位基因。4个地方品种在该基因座上都处于Hardy-Weinberg平衡状态(P>0.05)。青海高原牦牛和大通牦牛两个群体处于高度多态(PIC>0.5),甘南牦牛和天祝白牦牛处于中度多态(0.25<PIC<0.5)。

AT1R基因多态性与妊娠期高血压疾病相关性的Meta分析

目的探讨中国人群血管紧张素Ⅱ-1型受体（angiotensin Ⅱ type 1 receptor，AT1R）基因多态性与妊娠期高血压疾病发病的相关性。方法计算机检索中国期刊全文数据库、万方数据库、重庆维普数据库以及Pubmed数据库，检索时间为从建库至20t2年1月。按纳入、排除标准选择纳入有关中国人群AT1R A1166C基因多态性与妊娠期高血压疾病相关性的病例对照研究，评价纳入研究质量，并采用RevMan5．1和Stata11．0软件进行分析。结果共纳入11篇文献，病例组共计862例，对照组共计1142例。AT1R基因1166位点携带变异基因型（AC型＋CC型）的孕妇发生妊娠期高血压疾病的危险增加，合并OR值为2．11，95％c，为1．29～3．46。AT1R基因1166位点携带c等位基因的孕妇发生妊娠期高血压疾病的危险增加，合并OR值为2．02，95％c，为1．29—3．17。结论AT1 RA1166C基因多态性可能与中国人群妊娠期高血压疾病相关，C等位基因可能为妊娠期高血压疾病的致病基因。

IGF-1R基因在伴或不伴糖尿病的乳腺癌组织中的表达及其相关因素

目的:检测IGF-1R基因在伴或不伴糖尿病的乳腺癌组织中的表达,并探讨其与乳腺癌临床病理因素的关系。方法:利用免疫组织化学SP法检测68例不伴糖尿病的乳腺癌组织及相应的癌旁组织中IGF-1R蛋白的表达情况,与34例伴糖尿病的乳腺癌组织及相应的癌旁组织中IGF-1R蛋白的表达情况,并分析其与病人年龄、TNM分期、肿瘤大小及淋巴结转移等临床病理特征之间的相关性。结果:伴或不伴糖尿病的乳腺癌组织中IGF-1R蛋白的表达水平明显高于其相应的癌旁组织(P <0. 05)。伴或不伴糖尿病的乳腺癌组织中IGF-1R的表达与肿瘤的大小及TNM分期有关(P <0. 05),而与患者年龄无关。不伴糖尿病的乳腺癌组织中IGF-1R的表达与患者淋巴结转移状态有关(P <0. 05),而伴糖尿病的乳腺癌组织中IGF-1R的表达与患者淋巴结转移状态无关(P> 0. 05)。结论:IGF-1R基因在乳腺癌组织中的表达显著上调; IGF-1R基因的表达与肿瘤大小、TNM分期有关,而与年龄无关。不伴糖尿病的乳腺癌组织中IGF-1R的表达与患者淋巴结转移状态有关,而伴糖尿病的乳腺癌组织中IGF-1R的表达与患者淋巴结转移状态无关。

The R1947X mutation of NF1 causing autosomal dominant neurofibromatosis type 1 in a Chinese family

Neurofibromatosis type 1 is a common autosomal dominant disorder with a high rate of penetrance. It is caused by the mutation of the tumor suppressor gene NF1, which encodes neurofibromin. The main function of neurofibromin is down-regulating the biological activity of the proto-oncoprotein Ras by acting as a Ras-specific GTPase activating protein. In this study, we identified a Chinese family affected with neurofibromatosis type 1. The known gene NF1 associated with NF1 was studied by linkage analysis and by direct sequencing of the entire coding region and exon-intron boundaries of the NF1 gene. The R1947X mutation of NF1 was identified, which was co-segregated with affected individuals in the Chinese family, but not present in unaffected family members. This is the first report, which states that the R1947X mutation of NF1 may be one of reasons for neurofibromatosis type 1 in Chinese population.

乳酸片球菌R-4细菌素PA-1原核表达及其理化特性

为实现原核表达产出细菌素并检测其理化特性,作者将乳酸片球菌R-4细菌素pedA基因进行扩增回收,与pMD19-T载体连接后转入E.coli DH5α感受态细胞进行克隆。提取克隆后的pedA基因与表达载体pET-32a(+)连接,形成重组质粒pET-32a-pedA并转入E.coli BL21(DE3)感受态细胞,经异丙基硫代半乳糖苷诱导,乳酸片球菌R-4细菌素PA-1在大肠杆菌细胞进行表达。表达蛋白质经Ni-NTA柱纯化后,以金黄色葡萄球菌为指示菌检测其理化特性。结果表明,在E.coli BL21(DE3)细胞中成功表达相对分子质量为26000的乳酸片球菌R-4细菌素PA-1并完成纯化。纯化后的乳酸片球菌R-4细菌素PA-1在40~121℃作用20 min、在pH 2~12、紫外线照射0~10 h、过氧化氢酶作用2 h后,其抑菌范围分别为14.7~15.6 mm、14.0~16.5 mm、15.1~15.8 mm和14.9 mm,而分别经胃蛋白酶和胰蛋白酶作用2 h均失去抑菌作用。这表明乳酸片球菌R-4细菌素PA-1对高温、强酸强碱、紫外线和过氧化氢酶均具有较好的稳定性,而胃蛋白酶和胰蛋白酶会使其失活。

Induction of anti-hepatoma immunity by recombinant retrovirus expressing B7-1 /B7-2 costimulatory molecules

Objective: To construct recombinant R7-l/B7-2 retrovirus vectors and observe the effects of B7-l/R7-2 gene expression on in ho and in for immune response against against murine hepatoma. Methods: The recombinant retrovirus vectors expressing B7-1/B7-2 were constructed by gene cloning technology to produce retrovirus-infected PE501 and PA317 cell lines and murine hepatoma Hepal-6. The expression of R7-l/B7-2 was detected by fluorescence activated cell soning analysis (FACS). B7-l/B7-2 positive Hepal-6 Cell lines were used in inducing anti-hepatoma immunity in ho and in the. Results: In contrast to the excessive growth of parental Hemal-6 tumor, the growth of B7-l/B7-2-positive Hepal-6 inoculated into syngenic mice regressed. B7-1/R7-2-positive or cytokine-treated Hepal-6 alone could only induce mild cytototicity; in contrast, B7-1/B7-2-positive Hemal-6 treated with cytokine-stimulated spleen cells and activated the cytotoxicity effectively. Immunity in mice with R7-1/B7-2-positive tumor cells or cytokine-beated Hepal-6 only provided partial protection against parental Hepa1-6 tumor, whereas pretreatment of the transfected tumor cells with IFN-r and TNF-a induced complete immunity protection in vivo. Mice receiving inoculation of cytokine-treated B7-l/R7-2-positive Hemal-6 cells presented regression of the establoshed pental tUmor and survived for more than l00 d, while those untreated mice died within 40 d. Conclu sions: B7-l/R7-2 expression is necessary but not sufficient in inducing anti-hepatoma immune response, whereas it is efficient when combined with the beatment of IFN-γ and TNF-a.

Complement Gene Mutation and Ehlers-Danlos Syndrome

Background: Dental complications of Ehlers-Danlos syndrome (EDS) include periodontitis with gum fragility and inflammation, enamel hypoplasia with frequent caries, high palate with dental crowding, TMJ instability, sutural dehiscence or scarring, and insensitivity to anesthetics. Objective: Determine if EDS dental complications always define a specific type and genetic cause or if they can arise as a general consequence of altered inflammatory response in EDS. Method: We compared findings of a 58-year-old female with complement component 1R (C1R) gene mutation (c.1553A > T, p.Asp518Val) found by whole exome sequencing to 43 patients with C1R gene mutations ascertained because of periodontal disease and to 710 EDS patients conventially ascertained because of joint and skin laxity. Result: Female patients ascertained as periodontal EDS showed the expected higher frequency of periodontitis (96% versus 14%) but had similar frequencies of hypermobility (81% versus 90%) and some skin findings (84% versus 92% with skin fragility) as the general group and our female patient who shared their C1R gene change. Her oromandibular bone loss rather than gum disease may reflect the more carboxy-terminal position of her C1R gene mutation compared to those in the patients identified as periodontal EDS. Conclusion: While mutation of the C1R gene may predict more frequent periodontal, skin, and vascular complications, focus on an articulo-autonomic dysplasia process that includes mast-cell activation and altered inflammatory response rather than extreme EDS types will help dentists and other subspecialists identify all EDS patients and anticipate their frequent oral manifestations.