Coexistent Charcot-Marie-Tooth type 1A and type 2 diabetes mellitus neuropathies in a Chinese family

Charcot-Marie-Tooth disease type 1A(CMT1A) is caused by duplication of the peripheral myelin protein 22(PMP22) gene on chromosome 17. It is the most common inherited demyelinating neuropathy. Type 2 diabetes mellitus is a common metabolic disorder that frequently causes predominantly sensory neuropathy. In this study, we report the occurrence of CMT1 A in a Chinese family affected by type 2 diabetes mellitus. In this family, seven individuals had duplication of the PMP22 gene, although only four had clinical features of polyneuropathy. All CMT1 A patients with a clinical phenotype also presented with type 2 diabetes mellitus. The other three individuals had no signs of CMT1 A or type 2 diabetes mellitus. We believe that there may be a genetic link between these two diseases.     

Multiplexed imaging of surface enhanced Raman scattering nanotags in living mice using noninvasive Raman spectroscopy

Raman spectroscopy is a newly developed, noninvasive preclinical imaging technique that offers picomolar sensitivity and multiplexing capabilities to the field of molecular imaging. In this study, we demonstrate the ability of Raman spectroscopy to separate the spectral fingerprints of up to 10 different types of surface enhanced Raman scattering (SERS) nanoparticles in a living mouse after s.c. injection. Based on these spectral results, we simultaneously injected the five most intense and spectrally unique SERS nanoparticles i.v. to image their natural accumulation in the liver. All five types of SERS nanoparticles were successfully identified and spectrally separated using our optimized noninvasive Raman imaging system. In addition, we were able to linearly correlate Raman signal with SERS concentration after injecting four spectrally unique SERS nanoparticles either s.c. (R² = 0.998) or i.v. (R² = 0.992). These results show great potential for multiplexed imaging in living subjects in cases in which several targeted SERS probes could offer better detection of multiple biomarkers associated with a specific disease.     

全身多发性脂囊瘤

报告1例全身多发性脂囊瘤.患者男,40岁.因全身泛发囊肿30年就诊.无家族史.组织病理检查示真皮至皮下有不规则囊腔,囊壁为复层鳞状上皮,无颗粒层,与多个皮脂腺相连接.诊断:多发性脂囊瘤.患者未接受治疗.     

九个X染色体短串联重复基因座复合扩增体系的建立及遗传多态性

目的 发掘更多多态性高的X染色体短串联重复(X-chromsomme short tandem repeats,XSTR)基因座,以解决法医学实践中的特殊案例.方法 建立一组四色荧光复合扩增体系,同时检测DXS7133,DXS981,DXS7424,DXS6789,DXS7132,GATA165B12,DXS101,GATA31E08和DXS10011共9个X-STR基因座,采用ABI PRISM 3100遗传分析仪电泳和GeneMapper ID 3.1软件进行基因分型.结果 用此体系检测华南地区363个无关个体(251名男性,112名女性),9个基因座共检出111个等位基因,女性个体识别率为0.5837～0.9959;三联体非父排除率为0.4072～0.9511;多态性信息含量为0.4481～0.9531.结论 本体系中的基因座多态性高,高多态性的X-STR基因座复合扩增体系能为解决特殊的亲权鉴定案提供快速鉴定技术,是常染色体STR、Y-STR等鉴定方法的良好补充,在法医学实践和临床产前诊断中将有较好的实用价值.     

多重连接探针扩增检测Williams综合征微缺失

MLPA是一种简便快速检测缺失及重复突变的方法,该技术弥补了荧光原位杂交技术的不足,可用于实验室对Williams综合征的快速检测,具有一定临床诊断价值.     

一腓骨肌萎缩症家系临床及基因分析

目的分析一腓骨肌萎缩症家系的临床表现及不同基因检测方法的特点。方法收集一CMT家系8名成员临床资料,并应用等位基因特异性PCR-双酶切方法及多重连接依赖的探针扩增技术(MLPA)检测PMP22基因突变情况,同时选择60名性别、年龄无明显差异的健康人做为对照组。结果该家系中患病者以行走不稳、跨阈步态,伴有弓形足为主要临床表现。该家系中5名成员经等位基因特异性PCR-双酶切及MLPA方法均检测出PMP22基因重复序列,其中出现临床症状的有4名(Ⅱ3、Ⅱ9、Ⅱ11、Ⅲ7),未出现临床症状但基因检测结果示PMP22基因重复序列的为携带者有1名(Ⅲ5),家系中余3名成员及对照组60名均未见重复序列。结论基因检测在明确CMT诊断中起重要作用,且MLPA法筛查基因时操作更简便、灵敏度更高、特异性更好。     

Perineuritis in acute lyme neuroborreliosis

Perineuritis is an unusual cause of direct peripheral nerve injury. We describe the clinicopathologic features of a 56‐year‐old man with mononeuritis multiplex due to Lyme disease; sural nerve biopsy demonstrated florid perineuritis. Treatment with intravenous ceftriaxone resulted in marked neurologic improvement. This study supports the notion that perineuritis forms part of the pathogenesis in acute Lyme neuroborreliosis. Muscle Nerve, 2009     

利用多重数字PCR检测KRAS相关突变

 目的 建立多重数字PCR体系检测血浆细胞游离DNA(cell-free DNA, cfDNA)中KRAS第2外显子12、13密码子的7种突变。方法 构建7种KRAS突变型质粒用以建立多重数字PCR检测体系,以灵敏度、特异度和动态范围为主要参数评估体系的性能。利用该体系检测15例手术可切除的胰腺导管腺癌(pancreatic ductal adenocarcinoma, PDAC)患者血浆cfDNA中KRAS第2外显子12、13密码子突变情况,并与ARMs的检测结果进行比对。结果 自建的多重数字PCR在0.01%～10%的动态范围内线性良好。两个检测体系的灵敏度分别可达到0.025%和0.043%。15名PDAC患者组织中KRAS突变的阳性率达到100%。数字PCR检测血浆cfDNA所得的结果与组织结果的匹配率达到40%,ARMs检测组织和血浆cfDNA结果的匹配率为20%。15例样本中使用多重数字PCR检测到血浆cfDNA的最低丰度达到0.09%。结论 多重数字PCR具备高灵敏度和特异性,可用于准确定量外周血cfDNA中KRAS相关突变的水平。     

False-positive Y-microdeletion result for a fertile male caused by an alteration under a PCR primer

The pathogenic relationship between the presence of Y chromosomal microdeletions and male infertility is unclear. Nevertheless, a causal relationship is thought to be probable when loci are shown to be deleted in infertile males but are present in fertile males. Polymerase chain reaction (PCR) analysis of the Y chromosome is now routinely performed in the evaluation of the infertile male, although, until recently, there has been no consensus on how the diagnosis should be performed and which loci or markers should be analysed. The European Academy of Andrology (EAA) published guidelines for the molecular diagnosis of Y chromosomal microdeletions in 1999. Following these guidelines, our laboratory developed assays that incorporated the suggested primer pairs for the recommended Sequence Tagged Sites (STS). A number of fertile (n = 117), infertile (n = 17) and unknown samples (n = 20) were tested in our laboratory as part of the validation to provide a clinical assay. Two multiplex PCR assays were optimized, each of which examined STS markers in the centre of the AZFa, b and c regions of the Y chromosome. We correctly identified all but one of the 154 samples (according to the expected result based on fertility or previous testing at another laboratory). A single equivocal result was observed for a sample obtained from a known fertile male who appeared to be deleted for a single marker, sY84, in the AZFa region but not the adjacent marker, sY86. Follow-up analysis showed that proximal and distal markers within the same region (sY82 and sY98) were also present. Sequencing the region flanking and including the sY84 primer set revealed a single base alteration under the reverse primer, which probably caused the amplification failure. Furthermore, the sY84 sequence itself was present, as was the flanking sequence 50 bp on either side of both primers. This observation underlines the importance of using at least two closely linked STS markers for the reliable diagnosis of Y chromosome microdeletions as proposed by the EAA guidelines.     

Steatocystoma multiplex in four successive generations

A 16-year-old girl presented with multiple, yellowish, elastic, non-tender cysts on the face, trunk, arms and axillae for the last 3-4 years. On pricking, yellowish fluid could be expressed from the lesions. Clinically and histopathologically, the lesions were suggestive of steatocystoma multiplex. There was a family history of similar lesions in five members over four generations.