视网膜色素变性家系的产前分子诊断

目的：对1例常染色体显性遗传视网膜色素变性家系患者所怀胎儿进行产前分子诊断。方法：应用聚合酶链反应（PCR）和直接测序技术法，对一常染色体显性遗传视网膜色素变性（ADRP）家系成员的所有现存人员的视紫红质基因的外显子进行测序分析。在采用STR位点分析方法排除母体基因组DNA污染后，应用DNA序列测定对胎儿-羊水基因组DNA进行分析。结果：该家系的25名成员中12名患者有视紫红质基因（rhodopsin，RHO）的512C〉T（P171L）突变，均呈杂合子，该错义突变使密码子171由CCA变成CTA。而未受累者的视紫红质基因表现为野生型。对该家系成员进行产前诊断，发现胎儿具有同种致病性突变。结论：视紫红质基因RHO的一种已知突变512C〉T（P171L）是该家系的病因，胎儿带P171L突变，产前诊断和早期干预能避免视网膜色素变性患儿的出生。     

The phenotypic expression of different mutations in transmissible familial Creutzfeldt-Jakob disease

Cases of familial Creutzfeldt-Jakob disease (CJD) with mutations in the PRNP gene were analyzed for distinctive clinico-pathological and experimental transmission characteristics. An insert mutation within the region of codons 51 to 91 was associated with a markedly early age at onset and prolonged course of illness. Point mutations at codons 178 and 200 were also associated with ages at onset, durations of illness, and clinical symptom profiles that differed from sporadic CJD. The age at onset of illness in each group was correlated with the length of incubation periods in primates inoculated with their brain tissue, suggesting that the early onset of familial CJD results not from a time shift of the initiating event, but from an accelerated pre-clinical (incubation) phase of disease, perhaps due to a more rapid formation of amyloid induced by a mutationally-altered precursor protein template.     

Familial Creutzfeldt-Jakob disease with temporal and spatial separation of affected members

Familial occurrence of three definitive and two possible cases of Creutzfeldt-Jakob disease (CJD) with temporal and spatial separation in the area of focal CJD accumulation in Slovakia is reported. Incubation period is 51 and 53 years respectively, if spatial and temporal separation of affected siblings is considered, and 51 years when the time interval between the death of the affected mother and the clinical onset in the first affected child is determined.Affected children tend to die at the same time (mean difference 3.3 years) and not at the same age (mean difference 6 years). Due to separation of the affected children, a possible common exposure to CID infection was limited to approximately seven years during their childhood. Potential endo- and exogenous risk factors and a possible mode of CJD transmission in the described family, as well as in the CJD focus, is discussed.     

Epidemiologic implications of Creutzfeldt-Jakob disease in a 19 year-old girl

A histopathologically-verified, clinically typical case of Creutzfeldt-Jakob disease (CJD) is described in a 19 year-old girl. Only 3 previous cases of CJD have been reported in adolescents, and one of these was iatrogenically transmitted, while another was familial. Epidemiologic investigation of the present case excluded a familial component, and provided no evidence for iatrogenic or natural case-to-case transmission, or of other environmental sources of viral contamination. Young patients such as this one serve to emphasize the obscurity that still sourrounds the epidemiology of CJD, and invite serious reconsideration of the possibilities of transmission by undetected virus carriers, or of the agent as a natural resident of human cells, replication of which might be triggered by non-infective (e.g., traumatic or mutational) environmental events.     

上海市2006-2012年克雅氏病病例监测

目的 了解2006——2012年上海市克雅氏病(CJD)监测病例的检测结果及流行病学特征。方法 分析上海市CJD监测网络中可疑CJD病例的临床和流行病学资料,采集病例脑脊液及血液标本检测14-3-3蛋白和129位氨基酸多态性及PRNP基因突变。应用EpiData 3．0软件建立数据库,使用SPSS 17．0软件分析。结果 2006-2012年上海市发现散发型CJD确诊病例1例,临床诊断病例56例,疑似病例17例;家族遗传型CJD确诊病例l例,临床诊断1例,均为E200K突变。病例分布无季节聚集性,历年报告病例数保持稳定。CJD病例居住地散在分布,但2例家 族遗传型CJD患者住址相近。确诊和临床诊断病例的平均年龄为62岁,大于疑似病例的年龄(56岁),差异有统计学意义。结论2006-2012年上海市CJD历年发病例数稳定,均以散发型为主,职业分布广泛,确诊和临床诊断病例的平均年龄大于疑似病例。     

Tubulovesicular structures in human and experimental Creutzfeldt-Jakob disease

Tubulovesicular structures (TVS) have been consistently observed in brain tissue of animals with transmissible spongiform encephalopathies such as natural and experimental scrapie, bovine spongiform encephalopathy, and experimental Creutzfeldt-Jakob disease (CJD). In this communication we demonstrate for the first time the presence of TVS in natural CJD. TVS were detected in all 3 CJD specimens. However, they were rare and were found only in one or two locations per grid. They were seen in distended pre- and postsynaptic terminals and measured approximately 35 nm in diameter, and they were smaller and of higher electron density than synaptic vesicles. Their occurrence in all types of spongiform encephalopathies irrespective of the affected host and the strain of infectious agent emphasizes their biological significance.Corresponding author.     

Variant Creutzfeldt-Jakob disease death, United States

The only variant Creutzfeldt-Jakob disease (vCJD) patient identified in the United States died in 2004, and the diagnosis was confirmed by analysis of autopsy tissue. The patient likely acquired the disease while growing up in Great Britain before immigrating to the United States in 1992. Additional vCJD patients continue to be identified outside the United Kingdom, including 2 more patients in Ireland, and 1 patient each in Japan, Portugal, Saudi Arabia, Spain, and the Netherlands. The reports of bloodborne transmission of vCJD in 2 patients, 1 of whom was heterozygous for methionine and valine at polymorphic codon 129, add to the uncertainty about the future of the vCJD outbreak.     

A retrospective study of Creutzfeldt-Jakob disease in Italy (1972–1986)

In a retrospective study of Creutzfeldt-Jakob disease (CJD) in Italy from 1972 to 1986, we found 79 cases which fulfilled the diagnostic criteria for CJD. The annual mortality rate was 0.09 cases per million inhabitants. In this series the female to male ratio was 2.59, a value significantly higher than that found in Italian population (1.05). The mean age at death was 62.1 ± 9.4 years and the mean duration of the disease was 5.3 ± 3.0 months. No familial cases of CJD were found in our series. Mental deterioration was present in all of our cases, myoclonus in 85% and the other clinical signs were present at a lower rate. Periodic EEG activity was found in 92% of the cases. Two patients had had neurological or ophthalmic surgery and 17% of our cases had undergone general surgery within 5 years prior to the clinical onset of CJD.     

Epidemiological surveillance of Creutzfeldt-Jakob disease in the United Kingdom

Systematic epidemiological surveillance of Creutzfeldt-Jakob disease was carried out in England and Wales covering the years 1970–1984. The results of this work provide a basis from which to assess any change in the pattern of Creutzfeldt-Jakob disease following the occurrence of Bovine Spongiform Encephalopathy. The methodology, early results and problems of the current systematic national survey of CJD, initiated in May 1990, are discussed.     

Creutzfeldt-Jakob disease among libyan jews

The focus of CJD among Jews of Libyan origin has been recognized for two decades, but the reasons underlying it were unknown. Prevailing views suggested transmission from sheep infected with scrapie. However, recent data show that in fact CJD in this ethnic group is a genetically determined disease due to a point mutation on the codon 200 of the prion protein gene. The clinical characteristics of CJD in this group, and particularly the less common periodic activity in the EEG, are reviewed. New findings include peripheral neuropathy of the demyelinating type in two cases, presumably due to involvement of Schwann cells. The pathophysiology of the disease includes, presumably, a focal post-translational modification of the prion protein, (predisposed by the mutation). Later, the disease progresses through cell-to-cell transmission.     

PrP amyloid plaques in Creutzfeldt-Jakob disease of short duration: immunohistochemical studies of 5 cases from Poland.

We report here PrP-immunohistochemistry performed on brains from CJD cases from Poland. Only one of five definitive CJD cases exhibited typical PrP-immunoreactive kuru-like plaques and this was case of a short duration. We thus confirm the low frequency of PrP plaques in CJD of Eastern and Central European origin.Corresponding author.     

Mechanism of the damage to myelinated axons in experimental Creutzfeldt-Jakob disease in mice: An ultrastructural study

We report the ultrastructural pathology of myelinated axons in mice infected experimentally with the Fujisaki strain of Creutzfeldt-Jakob disease (CJD). Initially the myelin sheath was separated into several concentric bands, and cellular processes penetrated between layers of myelin and lifted away the outermost lamella. Then a complicated labyrinth of the concentric cellular processes, clearly belonging to either astrocytes or macrophages, invested myelinated axons. In terminal stages axons completely denuded of myelin were seen in the center of concentric networks of cellular processes. Myelin remnants were seen within astrocytes and macrophages. We conclude that the mechanism(s) of damage to myelinated axons in CID may be similar to that operating in immunologically mediated demyelinating disorders.Corresponding author.     

Classification of sporadic Creutzfeldt-Jakob disease based on clinical and neuropathological characteristics

Creutzfeldt-Jakob disease (CJD) is a rare and fatal neurodegenerative disease of unknown cause. Patients are usually aged between 50 and 75 and typical clinical features include rapidly progressive dementia associated with myoclonus and a characteristic electroencephalographic pattern. Neuropathological examination reveals cortical spongiform change, hence the term 'spongiform encephalopathy'. Several statistical techniques were applied to classify patients with sporadic CJD (sCJD), based on clinical and neuropathological investigation. We focus on the classification of neuropathologically confirmed sCJD patients. In order to obtain a classification rule that correctly classifies this type of patients and at the same time controls the overall error rate, we apply several classification techniques, which in general, produce comparable results. The boosting method produces the best results and the variable 14-3-3 protein in cerebrospinal fluid plays the most important role in the prediction of neuropathologically confirmed sCJD.     

Risk of Creutzfeldt-Jakob disease in relation to animal spongiform encephalopathies: A collaborative study in Europe

This paper describes a study of the risk of Creutzfeldt-Jakob disease in various European countries. The objectives of the study are to investigate the frequency of Creutzfeldt-Jakob disease and other human spongiform encephalophaties in Europe in relation to animal spongiform encephalophaties, and to assess the risk of Creutzfeldt-Jakob disease in relation to genetic, occupational and nutritional factors. The study will consist of three parts: the establishment of registries of Creutzfeldt-Jakob disease on the basis of cases in the registries, and molecular genetic studies with material collected in the registries.     

Creutzfeldt-Jakob Disease: A Case Report and Differential Diagnoses

Sporadic Creutzfeldt-Jakob disease is a rare neurodegenerative disorder of unknown etiology that causes rapidly progressive dementia. This disease is uniformly fatal and most patients die within 12 months. Clinical findings include myoclonus, visual disturbances, and cerebellar and pyramidal/extrapyramidal signs in addition to rapidly progressive cognitive and functional impairment. These findings are all non-specific and it is often difficult and challenging to diagnose premortem because of low awareness and clinical suspicion.We present a 66-year-old woman with a 5-month history of rapidly progressive dementia. After a series of extensive diagnostic examinations and continuous follow-up, she was diagnosed with probable sporadic Creutzfeldt-Jakob disease based on Centers for Disease Control and Prevention (CDC) criteria, with key findings of rapidly progressive dementia, blurry vision, extrapyramidal signs (cogwheel rigidity), and abnormal hyperintensity signals on diffusion-weighted MRI. Her symptoms progressively worsened and she died 7 months after the onset. The postmortem brain autopsy demonstrated the presence of abnormal protease-resistant prion protein by Western Blot analysis.A literature review was performed on differential diagnoses that present with rapidly progressive dementia and thereby mimic sporadic Creutzfeldt-Jakob disease. These include Alzheimer''s disease, dementia with Lewy Bodies, frontotemporal dementia, meningoencephalitis, corticobasal degeneration, progressive supranuclear palsy, CADASIL, and paraneoplastic encephalomyelitis.     

Creutzfeldt-Jakob disease — clinical picture analysis

The early, late, and terminal features of (CJD) were analyzed, based on the clinical histories and picture evolution of 12 histologically-confirmed cases of CJD. The most essential features observed were sensormotor disintegration, and impairment of both mental and higher cortical functions, occurring in various combinations. On the basis of a sampling of early symptoms and signs we were able to make an early differential diagnosis.Corresponding author.     

Epidemiology of retinitis pigmentosa in the valencian community (Spain)

The purposes of this study are to determine the frequencies of the different genetic forms of retinitis pigmentosa and to perform segregation analysis in the different genetic subtypes. Retinitis pigmentosa was diagnosed in 263 persons from 132 families. The frequency of the autosomal recessive type was the highest (31.8%) while the X-linked type was very rare (1.5%). The frequency of autosomal dominant type was 14.4% and the simplex cases constituted half of the total cases of RP registered in our community. In conclusion, in our population the high proportion of simplex cases and the low number of X-linked families are noticeable. The result of segregation analysis showed good agreement with expectation in autosomal dominant and autosomal recessive families but no more than 60% of all simplex cases were autosomal recessive. The proportion of sporadic cases was estimated statistically to be 39.9% of the total simplex cases. © Wiley-Liss, Inc.     

Source of variant Creutzfeldt-Jakob disease outside United Kingdom

We studied the occurrence of variant Creutzfeldt-Jakob disease (vCJD) outside the United Kingdom in relation to the incidence of indigenous bovine spongiform encephalopathy (BSE) and to the level of live bovines and bovine products imported from the UK during the 1980s and the first half of the 1990s. Our study provides evidence that a country's number of vCJD cases correlates with the number of live bovines it imported from the UK from 1980 to 1990 (Spearman rank correlation coefficient [r(s)] 0.73, 95% confidence interval [CI] 0.42-0.89, p < 0.001). Similar correlations were observed with the number of indigenous BSE cases (r(s) 0.70, 95% CI 0.37-0.87, p = 0.001) and carcass meat imported from the UK from 1980 to 1996 (r(s) 0.75, 95% CI 0.45-0.89; p < 0.001) Bovine imports from the UK may have been an important source of human exposure to BSE and may have contributed to the global risk for disease.     

Barriers to Creutzfeldt-Jakob disease autopsies, California

Creutzfeldt-Jakob disease (CJD) surveillance relies on autopsy and neuropathologic evaluation. The 1990-2000 CJD autopsy rate in California was 21%. Most neurologists were comfortable diagnosing CJD (83%), but few pathologists felt comfortable diagnosing CJD (35%) or performing autopsy (29%). Addressing obstacles to autopsy is necessary to improve CJD surveillance.