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Karen Buysse Barbara Delle Chiaie Rudy Van Coster Bart Loeys Anne De Paepe Geert Mortier Frank Speleman Bj?rn Menten 《European journal of medical genetics》2009,52(6):398-403
Molecular karyotyping has moved from bench to bedside for the genetic screening of patients with mental retardation and/or congenital anomalies. The commercial availability of high-resolution microarray platforms has significantly facilitated this process. However, the notion that copy number variants are also abundantly present in the general population challenges the interpretation of the clinical significance of detected copy number variants (CNVs) in these patients. Moreover, the awareness of incomplete penetrance and variable expression, exemplified by the inheritance of causal CNVs from apparently unaffected parents, has further blurred the boundary between benign and pathogenic variation. We analyzed 1001 patients using a large insert clone array (298 patients) and an oligonucleotide-based (703 patients) platform. In this cohort we encountered several examples of causal imbalances that could have been easily interpreted as benign variants when relying on established paradigms. Based on our experience and the pitfalls we encountered, we suggest a decision tree that can be used as a guideline in clinical diagnostics. Using this workflow, we detected 106 clinically significant CNVs in 100 patients, giving a diagnostic yield of at least 10%. Of these imbalances, 58 occurred de novo, 22 were inherited and 26 of unknown inheritance. This underscores that inherited CNVs should not be automatically disregarded as benign variants. Among the clinically relevant CNVs were 11 single-gene aberrations, highlighting the power of high-resolution molecular karyotyping to identify causal genes. 相似文献
74.
Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease 总被引:5,自引:2,他引:5
The allelic frequency of the gene for the K variant of
butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age
> 65 years) histopathologically diagnosed Alzheimer's disease (AD),
which was higher than the frequencies in 104 elderly control subjects
(0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed
cases of other dementia (0.10). The association of BCHE-K with late-onset
AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E
gene (APOE), among whom the presence of BCHE-K gave an odds ratio of
confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years
and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers
over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset
AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on
chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene
for late-onset AD.
相似文献
75.
R Bahl DJ Murphy B Strachan 《BJOG : an international journal of obstetrics and gynaecology》2009,116(2):319-326
Objectives The objectives of this study were to define the components of a skilled low-cavity non-rotational vacuum delivery (occiput anterior, vertex at station +2 or below and less than 45-degree rotation from midline) and to facilitate the transfer of skills from expert to trainee obstetricians.
Design Qualitative study using interviews and video recordings.
Setting Two university teaching hospitals (St Michael's Hospital, Bristol, and Ninewell's Hospital, Dundee).
Participants Ten obstetricians and eight midwives identified as experts in conducting or supporting operative vaginal deliveries.
Methods Semi-structured interviews were carried out using routine clinical scenarios. The experts were also video recorded conducting low-cavity vacuum deliveries in a simulation setting. The interviews and video recordings were transcribed verbatim and analysed using thematic coding. The anonymised data were independently coded by three researchers and compared for consistency of interpretation. The experts reviewed the coded interviews and video data for respondent validation and clarification. The themes that emerged following the final coding were used to formulate a list of skills.
Main outcome measures Key technical skills of a low-cavity non-rotational delivery.
Results The final list included detailed technical skills required for conducting a low-cavity vacuum delivery. The combination of semi-structured interviews and simulation videos allowed the formulation of a comprehensive skills tool for future evaluation.
Conclusion This explicitly defined skills list could aid trainees understanding of the technique of low-cavity vacuum delivery. This is an important first step in evaluating clinical competence in intrapartum procedures. 相似文献
Design Qualitative study using interviews and video recordings.
Setting Two university teaching hospitals (St Michael's Hospital, Bristol, and Ninewell's Hospital, Dundee).
Participants Ten obstetricians and eight midwives identified as experts in conducting or supporting operative vaginal deliveries.
Methods Semi-structured interviews were carried out using routine clinical scenarios. The experts were also video recorded conducting low-cavity vacuum deliveries in a simulation setting. The interviews and video recordings were transcribed verbatim and analysed using thematic coding. The anonymised data were independently coded by three researchers and compared for consistency of interpretation. The experts reviewed the coded interviews and video data for respondent validation and clarification. The themes that emerged following the final coding were used to formulate a list of skills.
Main outcome measures Key technical skills of a low-cavity non-rotational delivery.
Results The final list included detailed technical skills required for conducting a low-cavity vacuum delivery. The combination of semi-structured interviews and simulation videos allowed the formulation of a comprehensive skills tool for future evaluation.
Conclusion This explicitly defined skills list could aid trainees understanding of the technique of low-cavity vacuum delivery. This is an important first step in evaluating clinical competence in intrapartum procedures. 相似文献
76.
在一项随机、平行分组的开放试验中,27例妊娠糖尿病妇女(年龄30.7±6.3岁,HbA1c〈7%)随机分为门冬胰岛素治疗组(餐前5分钟注射)和常规人胰岛素治疗组(餐前30分钟注射)。试验时间为从诊断妊娠糖尿病(18~28周)至产后6周。研究期间两组的总体血糖水平均控制良好(试验开始和结束时HbA1c≤6%)。进餐试验时,试验6周时的平均血糖水平(门冬胰岛素组4.2±0.57mmol/L,常规人胰岛素组4.8±0.86mmol/L)略低于试验0周时(门冬胰岛素组4.9±0.59mmol/L,常规人胰岛素组5.1±0.36mmol/L)。 相似文献
77.
78.
Vorozole,a specific non-steroidal aromatase inhibitor 总被引:2,自引:0,他引:2
Summary Vorozole, the (+)-(S)-isomer of a new triazole compound, is a potent and selective aromatase inhibitor.In vitro, the compound is over a thousandfold more active than aminoglutethimide.In vivo, the compound very potently inhibits ovarian, peripheral, and tumoral aromatase. Vorozole shows anin vitro selectivity margin of 10,000-fold for aromatase inhibition as compared to inhibition of other P450- and non-P450-dependent reactions. This selectivity was confirmed in the ratin vivo. Vorozole, like ovariectomy, almost completely reduces tumor growth in the DMBA-induced mammary carcinoma model in the rat.In postmenopausal women, vorozole very potently inhibits peripheral conversion of androstenedione to estrone. After chronic administration, plasma estradiol levels are reduced while the levels of adrenal gluco- and mineralo-corticoids remain unchanged. Vorozole has excellent oral bioavailability and exerts linear, dose-proportional pharmacokinetics. 相似文献
79.
WPF Fetter J van Hof-van Duin W Baerts DJ Heersema M Wildervanck de Blécourt-Devilée 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(1):25-28
Visual development was studied in 10 very-low-birth-weight infants (less than 1500 g) with retinopathy of prematurity (ROP) stage 3+ who had been treated with cryocoagulation in both eyes. Binocular visual acuity (acuity cards method) and binocular visual fields (kinetic perimetry) were assessed repeatedly in the first year of life. At 12 months corrected age, visual acuity was normal in seven and impaired in three infants, who appeared to be severely myopic. Normal visual fields were found in eight infants at this age. The results indicate that cryotherapy in cases of ROP stage 3+ does not interfere with visual acuity development. The effect on visual field development needs further investigation. 相似文献
80.