Carrier Status (carrier + status)

Distribution by Scientific Domains

Selected Abstracts

Current Practice for Imparting Carrier Status Detected by Newborn Screening for Sickle Cell Disorders and Cystic Fibrosis in England

Hilda Parker

Is informed choice in genetic testing a different breed of informed decision-making?

A discussion paper
Traditionally genetic counselling has promoted a non-directive approach to patients' decision-making but the feasibility of this has been questioned. Unlike most branches of medicine, which are shifting away from a paternalistic model, genetic counselling is approaching shared decision-making from a different perspective. There are certain features of genetic counselling and genetic testing which may complicate the drive towards shared decision-making and informed choice: 1. Genetic test results can have broader implications than non-genetic test results. 2. Genetic test results may be perceived by the patient differently to non-genetic test results. 3. Carrier status for autosomal recessive conditions may be difficult for patients to conceptualize. 4. Decisions in genetic counselling are often multiple and sequential. 5. Most information in genetic counselling is based on probabilities and uncertainties. Each of these features is discussed in relation to achieving shared decision-making in genetic testing and the implications for genetic counsellors are described. The points raised, however, have broader implications for medicine as several of the features, although central to genetic testing, are not entirely unique. Lessons learnt from genetic testing and genetic counselling in achieving shared decision-making could help develop methods of promoting informed choice in other medical arenas such as cancer screening. [source]

Successful clearance of hepatitis B virus after allogeneic stem cell transplantation: beneficial combination of adoptive immunity transfer and lamivudine

Tetsuhiro Chiba
Abstract: We report a 38-yr-old male with acute lymphocytic leukemia (ALL), whose serological tests for the hepatitis B virus (HBV) before transplantation showed a chronic carrier status, and a liver biopsy specimen revealed chronic liver injury because of HBV. The patient underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from his sibling who was hepatitis B surface antibody (HBsAb) positive. He had received lamivudine treatment for the prophylaxis of HBV reactivation during cytotoxic chemotherapy, and lamivudine administration continued after transplantation. Successful engraftment was documented 3 wk after PBSCT, and clearance of the hepatitis B surface antigen (HBsAg) was observed 2 months after PBSCT. Liver function tests transiently showed a mild elevation of aminotransferases on day 25, although this returned to normal after the dose escalation of the immunosuppressive agent. We presume that the combination of adoptive immunity transfer by bone marrow transplantation (BMT) from an HBsAb-positive donor and antiviral drugs such as lamivudine is beneficial in clearing HBV in chronic carriers. [source]

Carrier testing in haemophilia A and B: adult carriers' and their partners' experiences and their views on the testing of young females

HAEMOPHILIA, Issue 3 2008
Summary., This is a descriptive study, which aims to report adult carriers' and their husbands/partners' experiences of carrier diagnosis and their views as to how these issues should be handled for the next generation. Following an initial pilot, 105 carriers and husbands/partners responded to a postal questionnaire. Most of the adult carriers had been tested because either they or their parents wanted to know their carrier status or they had a son diagnosed with haemophilia. The respondents agreed that the main reasons for testing young potential carriers should be either a family history of severe haemophilia or that the young person or her parents wanted to know her status. Forty per cent (35/87) believed the earliest age for carrier testing should be 0,9 years, 44% (38/87) 10,15 years and 16% (14/87) ,16 years. Respondents aged 18,39 years were more likely to be in favour of testing <2 years. If parents and teenagers disagreed, the majority of parents thought that a test should not be forced, consent refused or results withheld. Genetic counselling provides an important opportunity for parents, who want a very early genetic test, to explore their motivations and balance their desire to prepare and protect their daughter with her right to decide as a teenager. [source]

Assessment of the carrier status by pedigree analysis in some families from India

HAEMOPHILIA, Issue 5 2002
M. Singh
Summary., Pedigree analysis is an important tool to assess the carrier status of the females in the families of haemophiliac patients. A study was conducted on 85 families, of which 75 were of haemophilia type A and 10 of haemophilia type B. The probability values of the females being carriers were calculated by the Bayesian method. The results revealed that 45 mothers were genetic obligate carriers and the remaining 40 probable, hence the transmission was of familial nature in 45 families, whereas the remaining 40 were categorized as isolated cases. The probability values of 425 females were calculated and a wide range of probability values ranging from 0.0295 to 1 was observed. [source]

FGFR4 Gly388Arg polymorphism may affect the clinical stage of patients with lung cancer by modulating the transcriptional profile of normal lung

Felicia S. Falvella
Abstract The association of the fibroblast growth factor receptor 4 (FGFR4) Gly388Arg polymorphism with clinical stage and overall survival in a series of 541 Italian lung adenocarcinoma (ADCA) patients indicated a significantly decreased survival in patients carrying the rare Arg388 allele as compared to that in Gly/Gly homozygous patients [hazard ratio (HR) = 1.5; 95% confidence interval (CI) 1.1,1.9], with the decrease related to the association of the same polymorphism with clinical stage (HR = 1.8, 95% CI 1.3,2.6). By contrast, no significant association was detected in small series of either Norwegian lung ADCA patients or Italian lung squamous cell carcinoma (SQCC) patients. Single nucleotide polymorphisms of known FGFR4 ligands expressed in lung (FGF9, FGF18 and FGF19) were not associated with clinical stage or survival and showed no interaction with FGFR4. Analysis of gene expression profile in normal lungs according to FGFR4 genotype indicated a specific transcript pattern associated with the allele carrier status, suggesting a functional role for the FGFR4 polymorphism already detectable in normal lung. These findings confirm the significant association of the FGFR4 Gly388Arg polymorphism with clinical stage and overall survival in an Italian lung ADCA population and demonstrate a FGFR4 genotype-dependent transcriptional profile present in normal lung tissue. 2009 UICC [source]

C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease

G. Latkovskis
Summary C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1,, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(,511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(,174) and IL-6(,572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311,0.574) for CT or TT genotypes compared with 0.240 (0.107,0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l,1, respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115,0.388) for carriers and 0.421 (0.290,0.552) for non-carriers (CRP 1.79 and 2.64 mg l,1, respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients. [source]

Role of RFLP using TspRI for carrier detection in Glanzmann's thrombasthenia: a report on two families

Summary Glanzmann's thrombasthenia (GT) was diagnosed in two patients who presented with bleeding manifestations accompanied by absent platelet aggregation, secondary to adenosine-5'-diphosphate, adrenaline, arachidonic acid and collagen. Flow cytometry analysis for GPIIb/IIIa expression was done using CD61 and CD41 markers in these patients and their family members including siblings. The patients were sub typed as Type I as he had absent glycoproteins (GP) IIb/IIIa. Family studies by flow cytometry showed reduced GPII/IIIa expression in both the parents and one sibling. However, western blot showed abnormal GPIIb protein in all the family members including siblings. It is possible that abnormal GPIIb protein by western blot in family members may reflect their carrier status. Patients' DNA was analyzed for mutation in both the GPIIb and GPIIIa genes by conformational sensitive gel electrophoresis (CSGE), followed by sequencing. CSGE showed defect in exon 12 and the promoter region of GPIIb. By sequence, it was confirmed that both the mutations were homozygous one was c.1028T>C and the other one was M33320.1:g.951G>A. For one of these mutations, restriction fragment length polymorphism (RFLP) was developed to look for the same mutation in all the family members. RFLP was developed using a restriction enzyme (TspRI) against the patient's mutation, c.1028T>C in exon 12 of GPIIb gene. RFLP followed by gel electrophoresis revealed that the mutation was heterozygous in all the family members. The findings by RFLP were double confirmed by direct DNA sequencing of the exon 12 in all the family members. Thus, TspRI marker may be used as a RFLP marker to predict the carriers in GT families, if the patients' mutation status is identified. [source]

The Tumor Necrosis Factor Alpha ,308G>A Polymorphism Is Associated with Dementia in the Oldest Old

Helle Bruunsgaard MD
Objectives: To test the hypothesis that the tumor necrosis factor (TNF) ,308 G>A promoter gene polymorphism is a risk factor in age-related dementia and longevity. Design: A cross-sectional and a longitudinal study. Setting: A population-based sample of Danish centenarians. Participants: One hundred-year-old Danes (n=122) from "The Longitudinal Study of Danish Centenarians." Octogenarians (n=174) and healthy volunteers aged 18 to 30 (n=47) served as reference groups. Methods: Whether the distribution of TNF ,308 GG/GA/AA genotypes were different in centenarians than in younger age groups was investigated (Fischer exact test). Furthermore, whether the TNF ,308 G>A polymorphism was associated with the prevalence of dementia (logistic regression analysis), the plasma level of TNF-, (analysis of variance), and mortality in the following 5 years (Cox regression analysis) within the cohort of centenarians was tested. Results: The distribution of TNF ,308 genotypes was not different across the three different age groups, but the GA genotype was associated with decreased prevalence of dementia in centenarians. The few centenarians with AA carrier status had higher mortality risk and tended to show higher plasma levels of TNF-,, but the significance was questionable due to a low number of subjects with this genotype. Conclusion: It is possible that the TNF ,308 A allele is maintained during aging because subjects who are heterozygous for this polymorphism possess the optimal inflammatory response with regard to protection against age-related neurodegeneration. [source]

,-thalassaemia carrier detection by ELISA: A simple screening strategy for developing countries

M. Shyla Ravindran
Abstract The frequency of ,-thalassaemia in India ranges from 3.5% to 15% in the general population and of the 100,000 children born with thalassaemia major in the world, 10,000 are in India alone. Affected children do not die immediately, but treatment by regular transfusion is costly and leads to iron overload and death. Therefore, health services in lower-economic countries can sustain patients only if the numbers can be limited. Detecting carrier couples by simple blood test can prevent thalassaemia and at-risk couples can be identified and informed of their genetic risk before having children. A prevention programme including population screening, counselling, and prenatal diagnosis will markedly reduce the birth prevalence of affected individuals. Hemoglobin A2 (HbA2) measurement in human hemolysates has great significance, since its level can indicate ,-thalassaemia carrier status in otherwise healthy individuals. We have developed a rapid, simple, and inexpensive enzyme linked immunosorbent assay (ELISA) for the quantitation of HbA2, which can be used in carrier screening programmes in developing countries like India. In a limited trial for ,-thalassaemia carrier screening, the results obtained with ELISAs were compared with those obtained with the microcolumn chromatography method (r=0.89). J. Clin. Lab. Anal. 19:22,25, 2005. 2005 Wiley-Liss, Inc. [source]

TLR4 and IL-18 gene variants in aggressive periodontitis

Barbara Noack
Abstract Aim: We aimed to assess the association of different genotypes with increased aggressive periodontitis susceptibility by studying functional relevant variants in the pathogen-recognition receptor Toll-like receptor 4 (TLR4) and variants in the promoter region of the pro-inflammatory cytokine interleukin-18 (IL-18). Material and Methods: One hundred and eleven patients with aggressive periodontitis and 80 periodontally healthy controls were genotyped for four functional variants in the TLR4 gene (c.896A>G and c.1196C>T) and in the IL-18 promoter (c.,368G>C and c.,838C>A). The genotype and allele frequencies, as well as the frequency of combined genotypes were compared between study groups. Results: There were no statistical differences in genotype and allele frequencies within the four variants between the groups. All study subjects were further classified into carriers and non-carriers of at least one variant of both genes. The logistic regression analysis adjusted for gender and smoking showed no association between carrier status of at least one variant of both genes and periodontal status (OR=1.41, 95% CI: 0.43,4.70). Conclusions: Our results reject the hypothesis that functionally relevant IL-18 and TLR4 gene mutations have a major effect on aggressive periodontitis susceptibility alone or in combination. [source]

Characterization of susceptibility and carrier status of burbot, Lota lota (L.), to IHNV, IPNV, Flavobacterium psychrophilum, Aeromonas salmonicida and Renibacterium salmoninarum

M P Polinski
Abstract In this study, susceptibility and potential carrier status of burbot, Lota lota, were assessed for five important fish pathogens. Burbot demonstrated susceptibility and elevated mortality following challenge with infectious haematopoietic necrosis virus (IHNV) by immersion and to Aeromonas salmonicida by intraperitoneal (i.p.) injection. IHNV persisted in fish for at least 28 days, whereas A. salmonicida was not re-isolated beyond 17 days post-challenge. In contrast, burbot appeared refractory to Flavobacterium psychrophilum following intramuscular (i.m.) injection and to infectious pancreatic necrosis virus (IPNV) by immersion. However, i.p injection of IPNV resulted in re-isolation of virus from fish for the duration of the 28 day challenge. Renibacterium salmoninarum appeared to induce an asymptomatic carrier state in burbot following i.p. injection, but overt manifestation of disease was not apparent. Viable bacteria persisted in fish for at least 41 days, and bacterial DNA isolated by diagnostic polymerase chain reaction was detected from burbot kidney tissue 90 days after initial exposure. This study is the first to investigate susceptibility of burbot to selected fish pathogens, and this information will aid in efforts to culture and manage this species. [source]

Cosegregation of a Factor VIII Microsatellite Marker with Mild Hemophilia A in Golden Retriever Dogs

Marjory B. Brooks
Mild hemophilia A (factor VIII deficiency) was diagnosed in Golden Retrievers and pedigree studies were undertaken to test the cosegregation of an intragenic factor VIII marker with the disease phenotype. The study population consisted of 30 client-owned dogs (22 males and 8 females). Hemophilic males (n = 12) typically demonstrated prolonged bleeding after trauma or surgery rather than spontaneous hemorrhagic events. The affected males had a proportionate reduction in factor VIII coagulant activity (mean FVIII:C = 4%) and factor VIII protein concentration (mean FVIII:Ag = 3%). Twenty-five dogs (10 affected males, 8 clear males, 2 obligate carrier dams, and 5 suspect carrier daughters) were genotyped for a factor VIII microsatellite marker, with allele size assigned by an automated capillary electrophoresis system. Five distinct marker alleles were present in the study pedigree and a 300-base pair allele was found to segregate with the hemophilia A phenotype. The inheritance of the hemophilia-associated allele defined carrier status for 5 suspect daughters of obligate carrier dams. The limitations inherent to linkage analyses (ie, lack of access to key family members and homozygosity at the marker locus) did not preclude carrier detection in this pedigree. We conclude that genotype analysis for the intragenic factor VIII marker can aid in control of canine hemophilia A through enhanced carrier detection. [source]

Raised serum ferritin predicts non-response to interferon and ribavirin treatment in patients with chronic hepatitis C infection

S Distante
Abstract: Background/Aim: Previous studies have indicated that response to interferon therapy is inversely proportional to the amount of body iron stores. We have studied the relationship between serum ferritin, transferrin saturation, liver iron, presence of HFE-C282Y gene mutation and response to treatment in patients with chronic hepatitis C infection. Methods: Two hundred and fifty-six naive, HCV-RNA positive patients (60% males, median age 38 years, range 21,70) were treated with interferon and ribavirin for 6 months. Iron indices and the presence of the C282Y mutation were measured. In 242 (94%) patients iron deposition were determined by Perls staining method. Patients with negative HCV-RNA at 6 months after the end of treatment were defined as sustained viral responders. Results: Non-responders (n = 127) had significantly higher median s-ferritin values compared with sustained viral responders (130 g/L vs. 75 g/L P < 0.001). There was no difference in transferrin saturation among the two response groups. Only 23% (4/7) of patients with Perls grade 1 in liver biopsies responded to treatment vs. 54% (122/225) patients without iron deposition (P = 0.02), however, 10/13-non-responders had HCV genotype one. Two patients (0.8%) were homozygous for the C282Y mutation, 36 patients were heterozygous (14%). Among mutation carriers 26/38 achieved sustained response compared with 102/216 non-carriers (68% vs. 48%, P = 0.02). In a multivariate analysis s-ferritin (P = 0.030) and C282Y carrier status (P = 0.012) remained independent predict of sustained response. Conclusions: Raised s-ferritin values predicate non-response to interferon-ribavirin therapy in hepatitis C patients. Response rate in C282Y mutation carriers seems greater than in non-carriers. [source]

Type I Glanzmann thrombasthenia: Most common subtypes in North Indians

M. Kannan
Abstract The expression of GPIIb/IIIa on the platelet surface was assessed in 10 patients with Glanzmann thrombasthenia and their families by flow cytometry to determine the common subtype in North Indians. Glanzmann thrombasthenia was diagnosed in patients with bleeding manifestations accompanied by absent/reduced platelet aggregation, secondary to ADP, ADR, arachidonic acid, and collagen. Flow cytometry revealed variable GPIIb/IIIa expression by CD61 and CD41 in patients with Glanzmann thrombasthenia on the basis of CD61 levels, six patients were subtyped as type I because they had absent GPIIb/IIIa, three patients were subtyped as type II because their GPIIb/IIIa levels varied from 7.72% to 20.40%, and one patient was diagnosed as type III, because his clot retraction was 60% and GPIIb/IIIa was 46.0% of normal. Four fathers, three mothers, and five siblings were found to have GPIIb/IIIa levels less than 35% of normal. It is possible that low GPIIb/IIIa levels in family members may reflect their carrier status. It is postulated that flow cytometric estimation of GPIIb/IIIa in parents/siblings may detect carrier status in Glanzmann thrombasthenia. Am. J. Hematol. 74:139,141, 2003. 2003 Wiley-Liss Inc. [source]

Alpha 1 antitrypsin deficiency alleles are associated with joint dislocation and scoliosis in Williams syndrome,

Colleen A. Morris
Abstract Elastin haploinsufficiency is responsible for a significant portion of the Williams syndrome (WS) phenotype including hoarse voice, supravalvar aortic stenosis (SVAS), hernias, diverticuli of bowel and bladder, soft skin, and joint abnormalities. All of the connective tissue signs and symptoms are variable in the WS population, but few factors other than age and gender are known to influence the phenotype. We examined a cohort of 205 individuals with WS for mutations in SERPINA1, the gene that encodes alpha-1-antitrypsin (AAT), the inhibitor of elastase. Individuals with classic WS deletions and SERPINA1 genotypes PiMS or PiMZ were more likely than those with a SERPINA1 PiMM genotype to have joint dislocation or scoliosis. However, carrier status for AAT deficiency was not correlated with presence of inguinal hernia or with presence or severity of SVAS. These findings suggest that genes important in elastin metabolism are candidates for variability in the connective tissue abnormalities in WS. 2010 Wiley-Liss, Inc. [source]

Attitudes towards prenatal diagnosis and termination of pregnancy for thalassaemia in pregnant Pakistani women in the North of England

Shenaz Ahmed
Abstract Objectives Most births of children affected with ,-thalassaemia major in the United Kingdom are to parents of Pakistani origin. A popular explanation for this is that Pakistanis decline termination of pregnancy on religious grounds. However, various factors influence people's attitudes towards prenatal diagnosis and termination of pregnancy, which have not been investigated in a UK Pakistani sample. This study is aimed at exploring the attitudes of pregnant Pakistani women towards prenatal diagnosis and termination of pregnancy for ,-thalassaemia major in the North of England. Methods Forty-three pregnant women tested for thalassaemia carrier status were interviewed following receipt of their test results. Interviews were analysed using the grounded theory approach. Results Findings showed: (1) women's awareness of and attitudes towards prenatal diagnosis; (2) the relationship between attitudes towards prenatal diagnosis and termination of an affected foetus; (3) the relationship between attitudes towards termination of pregnancy and religious beliefs, perceptions of severity of the condition, influence of significant others, and (4) the impact of gestational age at the time of the offer of termination of pregnancy. Conclusions Pakistani women's attitudes towards prenatal diagnosis and termination of pregnancy are influenced by various factors, and therefore their religion should not be taken as a proxy for their attitudes either for or against termination of pregnancy. Copyright 2006 John Wiley & Sons, Ltd. [source]

First report of prenatal diagnosis of genetic congenital deafness in a routine prenatal genetic test

M. L. Santoro
Abstract Objective We aimed to screen for connexin26 gene (GJB2) mutations associated with autosomal recessive non-syndromic neurosensory deafness (NSRD) in a general risk population. Methods Screening for the most common connexin26 gene mutations was offered to all women undergoing a second-trimester amniocentesis for fetal karyotype analysis in our Center. After rapid DNA extraction from amniotic fluid, PCR amplification was performed and products analysed to detect mutations of GJB2 gene by a sequencing technique. In particular, we searched for the 20 most frequently reported mutations (out of the approximately 90 so far described) and for which there are commercially available tests. Results From a total of 4819 consecutive amniotic fluids examined, the following five different heterozygous mutations were detected: 35delG in 80 cases, 167delT in 3 cases and 1 occurrence of each of the following mutations: M34T, 35insG and W77R. From these data, a prevalence of 1 : 56 (1.78%) for the heterozygous condition can be estimated in the Mediterranean general risk population. The striking predominance of 35delG mutation is confirmed. In addition, we detected a homozygous 35delG mutation condition in a foetus of no risk parents. In this case, the early diagnosis permitted prompt application of an acoustic prosthesis allowing for cochlear implantation in due time, with significant improvement of the prognosis. Conclusions In a general risk population, a carrier status for congenital deafness can be observed in 1 : 56 (1.78%) amniotic fluids; this is mostly due to the presence of a 35delG mutation of the connexin26 gene. Occasional identification of homozygous states, although rare, allows the best therapeutic approach. Copyright 2003 John Wiley & Sons, Ltd. [source]

All in the family: Evaluation of the process and content of sisters' communication about BRCA1 and BRCA2 genetic test results,

Chanita Hughes
Abstract Despite the potential importance of family communication, little is known about the process and content of communicating BRCA1/2 test results to relatives. The objectives of this observational study were to describe the process and content of communicating BRCA1/2 test results to sisters, and to evaluate whether the proband's carrier status influenced communication outcomes. Participants were 43 women who were the first family member to have genetic testing (probands). Probands reported on communication outcomes for 81 sisters. Process and content variables were evaluated 1-month after receipt of BRCA1/2 test results using the Family Communication Questionnaire (FCQ). Overall, BRCA1/2 test results were communicated to 85% of sisters, and carriers communicated their results to significantly more sisters compared to uninformative (96% vs. 76%, FET,=,0.02). The most important reason for communicating results was to provide genetic risk information; however, compared to uninformatives, carriers communicated their results to significantly more sisters to obtain emotional support (74%) and to get advice about medical decisions (42%) (FET,=,0.001). Carriers also discussed the possibility of discrimination and recommendations for cancer management with significantly more sisters. Among sisters to whom BRCA1/2 test results were not communicated, the most important reason for not sharing test results was because of emotionally distant relationships. The results of this study suggest that probands are likely to quickly communicate their BRCA1/2 test results to relatives and that although needs for social support may motivate family communication, emotionally distant relationships may be a barrier to communication with relatives. 2001 Wiley-Liss, Inc. [source]

Heterozygote Carrier Testing in High Schools Abroad: What are the Lessons for the U.S.?

Lainie Friedman Ross M.D., Ph.D.Article first published online: 23 NOV 200
The main value of carrier detection in the general population is to determine reproductive risks. In this manuscript I examine the practice of providing carrier screening programs in the school setting. While the data show that high school screening programs can achieve high uptake, I argue that this may reflect a lack of full understanding about risks, benefits, and alternatives, and the right not to know. It may also reflect the inherent coercion in group testing, particularly for adolescents who are prone to peer pressure. The problem of carrier screening in the schools is compounded when the condition has a predilection for certain groups based on race, ethnicity or religion. I examine programs around the world that seek to test high school students for Tay Sachs and Cystic Fibrosis carrier status. I argue that carrier programs should be designed so as to minimize stigma and to allow individuals to refuse. The mandatory school environment cannot achieve this. Rather, I conclude that screening programs should be designed to attract young adults and not adolescents to participate in a more voluntary venue. [source]

Intra-operative cell salvage and sickle cell carrier status

ANAESTHESIA, Issue 6 2010
L. J. Hulatt
No abstract is available for this article. [source]

A Method for Estimating Penetrance from Families Sampled for Linkage Analysis

BIOMETRICS, Issue 4 2006
Yuanjia Wang
Summary When a gene variant is discovered to segregate with a disease, it may be of interest to estimate the risk (or the age-specific risk) of the disease to carriers of the variant. The families that contributed to the discovery of the variant would typically contain multiple carriers, and so, especially if the variant is rare, might prove a valuable source of study subjects for estimation of the risk. These families, by virtue of having brought the gene in question to the attention of researchers, however, may not be representative of the relationship between carrier status and the risk of the disease in the population. Using these families for risk estimation could bias the observed association between the variant and the risk. The purpose here is to present an approach to adjusting for the potential bias while using the families from linkage analysis to estimate the risk. [source]

Cognitive effects of memantine in postmenopausal women at risk of dementia: a pilot study

T. E. Wroolie
Background,,, To determine the effects of memantine on cognition in a normal population of postmenopausal women with putative risk factors for Alzheimer's disease (AD) using a built-in control for the genetic risk factor for AD (apoE-,4 status). Methods,,, A prospective, open-label, 6-month pilot medication trial with memantine and follow-up after discontinuance conducted at the Center for Neuroscience in Women's Health, Stanford University School of Medicine. Neuropsychological data were collected on 22 community-dwelling postmenopausal women (11 apoE-,4 carriers and 11 apoE-,4 non-carriers) with at least one putative risk factor for AD. Results,,, ApoE-,4 status was not a significant predictor of change in neuropsychological performance. Changes associated with memantine treatment for entire sample included significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal. A positive medication effect was noted with executive functions and possibly category fluency. Trend-level improvements were seen in motor dexterity of the non-dominant hand and maintained even after drug discontinuance. Conclusions,,, Treatment with memantine appeared to have differential effects on cognitive performance in a population of women with putative risk factors for AD. ApoE-,4 carrier status did not account for observed changes in cognition. [source]