脆性X染色体综合征家系遗传学分析

对一个脆性X染色体阳性家系进行了调查,用缺叶酸培养基(TC199)检查2名患者,脆性X检出率分别为13％,19％,本家系内尚有1名男性携带者,提示该家系脆性X染色体综合征不属于典型的X连锁隐性遗传。     

Mental retardation with rare fragile site expressed at 2q11

Several rare autosomal folate sensitive fragile sites were reported in individuals with mental retardation, neurological abnormalities, and multiple congenital malformations. Only three of them: fra(11)(q22.3), fra(X)(q27.3) and fra(X)(q28), are known to be associated with mental retardation and phenotypic abnormalities. A possible association of the other rare fragile sites with idiopathic mental retardation is still being discussed. Here, a girl who has a fragile site at 2q11 with minor congenital anomalies and mental retardation is presented. This case has recalled the question of idiopathic mental retardation that might be the clinical expression of rare FSFS. Fragility was observed at 2q11 with a frequency of 3% in her cells along with a partial endoreduplication at 2 q11→qter.     

The molecular role of Fra-1 and its prognostic significance in human esophageal squamous cell carcinoma

BACKGROUND:

The expression of Fra‐1 (Fos related antigen 1) involves tumor progression and invasion, and its gene ablation could suppress the invasive phenotypes of human tumor cells. The authors investigated the significance of Fra‐1 expression in esophageal squamous cell carcinoma (ESCC) and studied the effect of its down‐regulation on cell proliferation, motility, and invasion.

METHODS:

Surgical specimens from 164 patients with ESCC were evaluated. Fra‐1 expression in the primary tumor along with metastatic lymph nodes was compared among various clinicopathological characteristics, and overall survival was analyzed. The rate and intensity of Fra‐1 immunoreactivity were also investigated. The molecular role of Fra‐1 was assessed by its down‐regulation in human ESCC cell lines.

RESULTS:

Fra‐1 expression was positive in 127 (77.4%) ESCC patients. Immunoreactivity was localized to the marginal areas of the ESCC tumors. Positive Fra‐1 expression correlated with depth of tumor, lymph node metastasis, stage, and infiltrative growth pattern. A significant difference was seen in the survival between tumors with and without Fra‐1, and positive Fra‐1 expression was revealed to be an independent factor related to poor prognosis. Patients with metastatic lymph nodes with positive Fra‐1 expression presented decreased survival compared with negative Fra‐1 expression. After the down‐regulation of Fra‐1 expression, a significant decrease in cell proliferation, motility, and invasion was observed.

CONCLUSIONS:

This study demonstrated ESCC patients positive for Fra‐1 to be associated with poor prognosis. The findings also suggest that Fra‐1 regulation may play an important role in the progression of ESCC. Cancer 2011. © 2011 American Cancer Society.     

Anticardiolipin Antibody in Patients with Behçet's Disease with and without Vascular Thrombosis

Objective: The clinical value of IgG anticardiolipin antibody in patients with Behçet's disease with or without vascular thrombosis was evaluated.   Methods: IgG isotype of anticardiolipin (aCL) antibody was assessed in 40 Behçet's disease (BD) patients with venous or arterial thrombosis, 40 BD patients without venous or arterial thrombosis and 80 healthy subjects as controls. The levels of IgG aCL were determined by an indirect ELISA method. Color Doppler Sonography, Magnetic Resonance Imaging and conventional angiography were the procedures used for other clinical evaluations. Results: Out of 40 patients with vascular thrombosis, 20(50%) were positive for low to moderate level of IgG aCL. In patients without thrombosis 22(55%) were positive for low to moderate level of IgG aCL while in none (0%) of the healthy subjects the IgG aCL was positive, neither low nor moderate. The number of patients with headache but having a normal cerebral magnetic resonance imaging (MRI), was higher in anticardiolipin positive patients without vascular thrombosis as compared to those with vascular thrombosis, (P = 0.001). Arthritis was noticed in both patents groups. 15% of aCL positive patients without thrombosis had arthritis as compared to none in aCL negative patients without thrombosis (P = 0.02).   Conclusion: The results of this study indicate that although the frequency of IgG aCL was found to be higher in Iranian patients with BD in comparison with the previous reports, except in arthritis the observed elevated IgG aCL does not correlate with clinical disease manifestations, or vascular thrombotic complications.     

Identification of the human/mouse syntenic common fragile site FRA7K/Fra12C1--relation of FRA7K and other human common fragile sites on chromosome 7 to evolutionary breakpoints

Common fragile sites (CFSs) are expressed as chromosome gaps in cells of different species including human and mouse as a result of the inhibition of DNA replication. They may serve as hot spots for DNA breakage in processes such as tumorigenesis and chromosome evolution. Using multicolor fluorescence in situ hybridization mapping, the authors describe here human CFS FRA7K on chromosome band 7q31.1 and its murine homolog Fra12C1. Within the syntenic FRA7K/Fra12C1 region lies the IMMP2L/Immp2l gene with a size of 899/983 kb. The authors further mapped 2 amplification breakpoints of the breast cancer cell line SKBR3 to the CFSs FRA7G and FRA7H. The 5 molecularly defined CFSs on chromosome 7 do not preferentially colocalize with synteny breaks between the human and mouse genomes and with intragenomic duplications that have occurred during chromosome evolution. In addition, in contrast to all currently reported data, CFSs in chromosome band 7q31 do not show increased DNA helix flexibility in comparison with control regions without CFS expression.     

脆性X综合征的细胞遗传学研究

本研究从１０个Ｘ－连锁智力低下家系中，经细胞遗传学检查，检测出５个Ｆｒａ（Ｘ）综合征家系，共１５名患者和携带者检查发现：１、不同成份培养液对脆性Ｘ表达有影响。２、活性Ｘ染色体Ｘｑ２７迟复制与Ｆｒａ（Ｘ）综合征患者智力密切相关。３、Ｆｒａ（Ｘ）染色体的活性与女性携带者的智力有一定的关系     

The ubiquitin proteasome system in neurodegenerative diseases: Culprit,accomplice or victim?

A shared hallmark for many neurodegenerative disorders is the accumulation of toxic protein species which is assumed to be the cause for these diseases. Since the ubiquitin proteasome system (UPS) is the most important pathway for selective protein degradation it is likely that it is involved in the aetiology neurodegenerative disorders. Indeed, impairment of the UPS has been reported to occur during neurodegeneration. Although accumulation of toxic protein species (amyloid β) are in turn known to impair the UPS the relationship is not necessarily causal. We provide an overview of the most recent insights in the roles the UPS plays in protein degradation and other processes. Additionally, we discuss the role of the UPS in clearance of the toxic proteins known to accumulate in the hallmarks of neurodegenerative diseases. The present paper will focus on critically reviewing the involvement of the UPS in specific neurodegenerative diseases and will discuss if UPS impairment is a cause, a consequence or both of the disease.