A novel medical approach for qualifying DNA variants found by whole exome sequencing (WES) facilitates discovery of new gene-disease relationships and emphasizes that DNA change must be correlated with clinical findin...A novel medical approach for qualifying DNA variants found by whole exome sequencing (WES) facilitates discovery of new gene-disease relationships and emphasizes that DNA change must be correlated with clinical findings before having utility for diagnosis. Delineation of an arthritis-adrenaline disorder (AAD) process qualified variants in 23 genes as diagnostically useful in 727 patients having WES among 1656 with Ehlers-Danlos syndrome (EDS);these results distinguished them from 102 patients who had qualified gene variants among 728 with developmental disability. Excess maternal transmission of AAD by pedigree analysis plus 167 maternally versus 111 paternally transmitted DNA variants and 75 patients with only mitochondrial DNA variants suggest maternal influence on inheritance of AAD and its subsumed EDS types. Genes grouped by impact on different connective tissue elements showed variation in similar numbers of patients with hypermobile or classical EDS, benign joint hypermobility, or predominant dysautonomia: COL7A1, FLG acting on skin in 21 patients;SCN9A/10A/11A, POLG on nerve in 24;COL6A1/A2/A3, COL12 on muscle in 19;COL5A1/A2, FBN1, TGFB2/3, TGFBR1/2 on tissue matrix in 51;COL3A1, VWF on vessel in 18;COL1A1/A2, COL11A1/A2 acting on bone in 15 patients. Each gene group acts through a postulated articulo-autonomic dysplasia cycle to produce reciprocal tissue laxity and dysautonomia findings that transcend EDS types. This same tissue laxity-dysautonomia cycle acts to produce secondary complications in disorders ranging from distinctive connective tissue dysplasias to developmental disorders with hypotonia and acquired conditions with autonomic imbalance. Several altered genes were previously associated with neuromuscular disorders, foreshadowing a large myopathic EDS category that will incorporate many patients with hypermobility. The importance of muscle for joint constraint supports present exercise and future mesenchymal stem cell therapies, whether AAD is genetic or epigenetic from trauma, surgery, infla展开更多
BACKGROUND Known ocular manifestations of Alport syndrome include features such as anterior lenticonus and fleck retinopathy. Reports of keratoconus in such patients are limited. We report tomographic findings consist...BACKGROUND Known ocular manifestations of Alport syndrome include features such as anterior lenticonus and fleck retinopathy. Reports of keratoconus in such patients are limited. We report tomographic findings consistent with keratoconus in a patient with Alport syndrome.CASE SUMMARY A 52-year-old female was referred to our ophthalmology clinic with decreased vision and increased tearing. She was diagnosed with stage Ⅲ Alport syndrome two years prior. Upon examination she was found to have average keratometries of 48D bilaterally with tomographic evidence of keratoconus.CONCLUSION Although a rare presentation, concurrent Alport syndrome and keratoconus should be considered when reviewing the ocular health of Alport syndrome patients and appropriate management steps should be taken upon the diagnosis.展开更多
目的探讨氟暴露人群中，氟中毒与COLIXA3（the a3 chain of collagen Ⅸ）mRNA表达水平的关系，观察在地方性氟中毒的发病机制中COLIXA3基因所起的作用。方法2009年，选取新疆生产建设兵团农七师123团和128团确诊的轻度氟中毒患者12人...目的探讨氟暴露人群中，氟中毒与COLIXA3（the a3 chain of collagen Ⅸ）mRNA表达水平的关系，观察在地方性氟中毒的发病机制中COLIXA3基因所起的作用。方法2009年，选取新疆生产建设兵团农七师123团和128团确诊的轻度氟中毒患者12人为病例组，生活在氟中毒病区10年以上的6例健康人作为内对照组．生活在非氟中毒病区10年以上的6例健康人作为外对照组，采集静脉血，分离淋巴细胞，采用SYBR Green Ⅰ嵌合荧光法进行实时定量PCR，对氟骨症患者和对照组淋巴细胞中COLIXA3mRNA进行相对表达量的检测。结果病例组、内对照组、外对照组COLIXA3基因的相对表达量分别为2．16±0．62、1．06±0．09、1．05±0．12。病例组COLIXA3表达明显上调，高于内对照组和外对照组（P均〈0．05），内对照组与外对照组组间比较差异无统计学意义（P〉0．05）。结论过量氟可促进患者外周血淋巴细胞中COLIXA3mRNA的表达．达到对照组的2倍以上，可能有生物标志物意义。展开更多
文摘A novel medical approach for qualifying DNA variants found by whole exome sequencing (WES) facilitates discovery of new gene-disease relationships and emphasizes that DNA change must be correlated with clinical findings before having utility for diagnosis. Delineation of an arthritis-adrenaline disorder (AAD) process qualified variants in 23 genes as diagnostically useful in 727 patients having WES among 1656 with Ehlers-Danlos syndrome (EDS);these results distinguished them from 102 patients who had qualified gene variants among 728 with developmental disability. Excess maternal transmission of AAD by pedigree analysis plus 167 maternally versus 111 paternally transmitted DNA variants and 75 patients with only mitochondrial DNA variants suggest maternal influence on inheritance of AAD and its subsumed EDS types. Genes grouped by impact on different connective tissue elements showed variation in similar numbers of patients with hypermobile or classical EDS, benign joint hypermobility, or predominant dysautonomia: COL7A1, FLG acting on skin in 21 patients;SCN9A/10A/11A, POLG on nerve in 24;COL6A1/A2/A3, COL12 on muscle in 19;COL5A1/A2, FBN1, TGFB2/3, TGFBR1/2 on tissue matrix in 51;COL3A1, VWF on vessel in 18;COL1A1/A2, COL11A1/A2 acting on bone in 15 patients. Each gene group acts through a postulated articulo-autonomic dysplasia cycle to produce reciprocal tissue laxity and dysautonomia findings that transcend EDS types. This same tissue laxity-dysautonomia cycle acts to produce secondary complications in disorders ranging from distinctive connective tissue dysplasias to developmental disorders with hypotonia and acquired conditions with autonomic imbalance. Several altered genes were previously associated with neuromuscular disorders, foreshadowing a large myopathic EDS category that will incorporate many patients with hypermobility. The importance of muscle for joint constraint supports present exercise and future mesenchymal stem cell therapies, whether AAD is genetic or epigenetic from trauma, surgery, infla
文摘BACKGROUND Known ocular manifestations of Alport syndrome include features such as anterior lenticonus and fleck retinopathy. Reports of keratoconus in such patients are limited. We report tomographic findings consistent with keratoconus in a patient with Alport syndrome.CASE SUMMARY A 52-year-old female was referred to our ophthalmology clinic with decreased vision and increased tearing. She was diagnosed with stage Ⅲ Alport syndrome two years prior. Upon examination she was found to have average keratometries of 48D bilaterally with tomographic evidence of keratoconus.CONCLUSION Although a rare presentation, concurrent Alport syndrome and keratoconus should be considered when reviewing the ocular health of Alport syndrome patients and appropriate management steps should be taken upon the diagnosis.
文摘目的探讨氟暴露人群中，氟中毒与COLIXA3（the a3 chain of collagen Ⅸ）mRNA表达水平的关系，观察在地方性氟中毒的发病机制中COLIXA3基因所起的作用。方法2009年，选取新疆生产建设兵团农七师123团和128团确诊的轻度氟中毒患者12人为病例组，生活在氟中毒病区10年以上的6例健康人作为内对照组．生活在非氟中毒病区10年以上的6例健康人作为外对照组，采集静脉血，分离淋巴细胞，采用SYBR Green Ⅰ嵌合荧光法进行实时定量PCR，对氟骨症患者和对照组淋巴细胞中COLIXA3mRNA进行相对表达量的检测。结果病例组、内对照组、外对照组COLIXA3基因的相对表达量分别为2．16±0．62、1．06±0．09、1．05±0．12。病例组COLIXA3表达明显上调，高于内对照组和外对照组（P均〈0．05），内对照组与外对照组组间比较差异无统计学意义（P〉0．05）。结论过量氟可促进患者外周血淋巴细胞中COLIXA3mRNA的表达．达到对照组的2倍以上，可能有生物标志物意义。
