新疆地区维吾尔族成骨不全九例患儿基因型与表型分析

目的探讨新疆地区维吾尔族儿童成骨不全基因变异谱系及临床表型特点.方法回顾性分析2013年1月至2017年12月新疆医科大学第一附属医院儿科就诊的9例(男4例、女5例)维吾尔族成骨不全患儿的临床资料,按照经典Sillence分型进行临床分型.检测成骨不全相关基因,利用美国医学遗传学和基因组学协会指南、InterVar、Alamut功能软件评估变异致病性,分析基因变异谱系特点.结果9例患儿年龄3岁6月龄~15岁,临床表现为反复骨折、骨骼畸形、矮小、蓝巩膜、听力异常、牙本质发育不全、关节韧带松弛.其中成骨不全Ⅲ型6例、Ⅳ型3例.9例患儿中共发现3种基因(COL1A1、COL1A2和SERPINF1)的9个候选变异,其中5个变异位点为国际首次报道,经评估均为可能致病性变异.结论新疆维吾尔族成骨不全临床表型复杂多样,但均有骨折及骨骼畸形.基因型与国内外报道有差异,SERPINF1基因可能在维吾尔族人群中更为高发,维吾尔族成骨不全的遗传异质性及独特的基因变异谱系,进一步为成骨不全的基因型与表型相关性提供了依据.     

Phenotype profiling of patients with intellectual disability and copy number variations

BackgroundNowadays the microarray technology allows whole-genome analysis with a high resolution and performance for the genetic diagnosis in any patient with intellectual disability or autism spectrum disorder. However in the immediate future, with the development of massive sequencing systems for application at clinical diagnosis, it will be necessary to have clinical criteria to guide studies.AimTo perform an exhaustive clinical definition of patients with pathogenic copy number variations in order to establish the clinical criteria most suggestive of this kind of genomic rearrangements.MethodWe designed and implemented a database to collect 190 different clinical variables (pregnancy, neonatal, facial dysmorphism, congenital anomalies, neurological features and family history) in a series of 246 patients, with developmental delay/intellectual disability. All cases were studied with array comparative genomic hybridization.ResultsWe have found a pathogenic genomic imbalance in 73 patients. Frequency analysis of all clinical variables showed that growth disorder, abnormalities of hands, low-set ears and hypertelorism are the more frequent features among patients with genomic rearrangements. However other clinical features, such as genital abnormalities and aggressiveness, are more specifically associated with pathogenic copy number variations in spite of their low frequencies in the overall series, yielding higher statistical significance values than other traits.ConclusionsThe genotype–phenotype comparison may be useful to set in the future the main clinical manifestations associated with deletions, duplications and unbalanced translocations. Theses analyses will improve the clinical indications and protocols to implement genomic arrays in the genetic study of patients with neurodevelopment disorders.     

Unusual variability of PRRT2 linked phenotypes within a family

BackgroundMutations in the proline-rich transmembrane protein 2 (PRRT2) gene on chromosome 16p11.2 have recently been identified as a cause of paroxysmal kinesigenic dyskinesias (PKD), infantile convulsions and choreoathetosis (ICCA) syndrome or infantile convulsions (IC).AimsHere, we describe a family with four affected members. They all suffer from different diseases: febrile convulsion, epileptic seizures, PKD or headache.MethodsThe whole coding region of PRRT2 gene has been analyzed.ResultsMolecular testing revealed the PRRT2 gene mutation c649.delC in exon 2 for all three sibs as well as for the mother.ConclusionOur presented family case shows the great variability within PRRT2 linked phenotypes even within the same family. Further and more detailed studies will be needed before genetic findings enter into the daily diagnostic and the daily genetic counseling with all its consequences.     

口腔癌患者外周血树突状细胞的体外培养及表型分析

目的：研究口腔癌患者外周血单核细胞来源的树突状细胞（dendritic cell，DC）形态、表型，与正常人进行比较并分析其临床意义。方法：15例口腔癌患者（实验组）及正常人（对照组）外周血单核细胞经GMCSF，IL4及TNF-α诱导培养，获取成熟树突状细胞，光镜和电镜观察细胞形态，流式细胞仪检测细胞表型CD1a、CD83、CD80、CD86和HLA-DR的表达变化。结果：培养7d后，2组均诱导出典型形态和表型的树突状细胞，实验组CD83、CD1a的表达率较对照组低，差异有统计学意义（均P〈0．001），但CD86、CD80、HLADR表达率2组差异无统计学意义（均P〉0．05）。结论：口腔鳞癌患者外周血单核细胞来源的DC经细胞因子诱导培养，能扩增出较大量高纯度并保持功能活性的成熟DC，为进一步开展以DC为基础的生物治疗和研究打下了基础。     

Impact of Staphylococcus aureus phenotype and genotype on the clinical characteristics and outcome of infective endocarditis. A multicentre,longitudinal, prospective,observational study

ObjectiveWe aimed to evaluate the impact of Staphylococcus aureus phenotype (vancomycin MIC) and genotype (agr group, clonal complex CC) on the prognosis and clinical characteristics of infective endocarditis (IE).MethodsWe performed a multicentre, longitudinal, prospective, observational study (June 2013 to March 2016) in 15 Spanish hospitals. Two hundred and thirteen consecutive adults (≥18 years) with a definite diagnosis of S. aureus IE were included. Primary outcome was death during hospital stay. Main secondary end points were persistent bacteraemia, sepsis/septic shock, peripheral embolism and osteoarticular involvement.ResultsOverall in-hospital mortality was 37% (n = 72). Independent risk factors for death were age-adjusted Charlson co-morbidity index (OR 1.20; 95% CI 1.08–1.34), congestive heart failure (OR 3.60; 95% CI 1.72–7.50), symptomatic central nervous system complication (OR 3.17; 95% CI 1.41–7.11) and severe sepsis/septic shock (OR 4.41; 95% CI 2.18–8.96). In the subgroup of methicillin-susceptible S. aureus IE (n = 173), independent risk factors for death were the age-adjusted Charlson co-morbidity index (OR 1.17; 95% CI 1.03–1.31), congestive heart failure (OR 3.39; 95% CI 1.51–7.64), new conduction abnormality (OR 4.42; 95% CI 1.27–15.34), severe sepsis/septic shock (OR 5.76; 95% CI 2.57–12.89) and agr group III (OR 0.27; 0.10–0.75). Vancomycin MIC ≥1.5 mg/L was not independently associated with death during hospital nor was it related to secondary end points. No other genotype variables were independently associated with in-hospital death.ConclusionsThis is the first prospective study to assess the impact of S. aureus phenotype and genotype. Phenotype and genotype provided no additional predictive value beyond conventional clinical characteristics. No evidence was found to justify therapeutic decisions based on vancomycin MIC for either methicillin-resistant or methicillin-susceptible S. aureus.