CSF cutoffs for MCI due to AD depend on APOEε4 carrier status

SummaryThe point mutation Arg506->Gln of factor V was recently shown to be an important and relatively common genetic cause of venous thromboembolism. Using a DNA technique based on polymerase chain reaction, we surveyed the blood samples of 236 patients with ischaemic stroke or a transient ischaemic attack, 122 survivors of myocardial infarction and 137 control subjects for the presence of this mutation. Although the frequency of the factor V mutation in patients with arterial disease (4.5%) was not significantly different from that in healthy blood donors (2.9%), a carrier status for this mutant gene was associated with symptoms of migraine and relatively mild angiographic abnormalities among patients with cerebrovascular disease. A more extensive study addressing the occurrence and significance of the mutant factor V mutation in patients with vasospastic cerebrovascular diseases seems to be warranted.

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Prevalence of thrombophilic conditions and genetic carrier status in neuroischaemic form of diabetic foot

Angiology and vascular surgery ◽

10.33529/angio2019408 ◽

2019 ◽

Vol 25 (4) ◽

pp. 28

Author(s):

A. A. Poliantsev ◽

D. V. Frolov ◽

D. V. Linchenko ◽

V. S. Ovanenko ◽

Iu. A. D'iachkova

Keyword(s):

Diabetic Foot ◽

Carrier Status

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Diagnostic exome-based preconception carrier testing in consanguineous couples: results from the first 100 couples in clinical practice

Genetics in Medicine ◽

10.1038/s41436-021-01116-x ◽

2021 ◽

Author(s):

Suzanne C. E. H. Sallevelt ◽

Alexander P. A. Stegmann ◽

Bart de Koning ◽

Crool Velter ◽

Anja Steyls ◽

...

Keyword(s):

Autosomal Recessive ◽

Rare Variants ◽

Clinical Care ◽

Carrier Testing ◽

Carrier Status ◽

Routine Diagnostics ◽

Affected Offspring ◽

Pathogenic Variants ◽

Increased Risk ◽

Genetics And Genomics

Abstract Purpose Consanguineous couples are at increased risk of being heterozygous for the same autosomal recessive (AR) disorder(s), with a 25% risk of affected offspring as a consequence. Until recently, comprehensive preconception carrier testing (PCT) for AR disorders was unavailable in routine diagnostics. Here we developed and implemented such a test in routine clinical care. Methods We performed exome sequencing (ES) for 100 consanguineous couples. For each couple, rare variants that could give rise to biallelic variants in offspring were selected. These variants were subsequently filtered against a gene panel consisting of ~2,000 genes associated with known AR disorders (OMIM-based). Remaining variants were classified according to American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, after which only likely pathogenic and pathogenic (class IV/V) variants, present in both partners, were reported. Results In 28 of 100 tested consanguineous couples (28%), likely pathogenic and pathogenic variants not previously known in the couple or their family were reported conferring 25% risk of affected offspring. Conclusion ES-based PCT provides a powerful diagnostic tool to identify AR disease carrier status in consanguineous couples. Outcomes provided significant reproductive choices for a higher proportion of these couples than previous tests.

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Real-Time PCR as an Alternative Technique for Detection of Dermatophytes in Cattle Herds

Animals ◽

10.3390/ani11061662 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1662

Author(s):

Dominik Łagowski ◽

Sebastian Gnat ◽

Aneta Nowakiewicz ◽

Aleksandra Trościańczyk

Keyword(s):

Light Microscopy ◽

Real Time ◽

Real Time Pcr ◽

Direct Analysis ◽

Carrier Status ◽

The Real ◽

Detection Techniques ◽

Direct Light ◽

Microscopy Analysis ◽

Cattle Herds

Dermatophytes are filamentous fungi with the ability to digest and grow on keratinized substrates. The ongoing improvements in fungal detection techniques give new scope for clinical implementations in laboratories and veterinary clinics, including the monitoring of the disease and carrier status. The technologically advanced methods for dermatophyte detection include molecular methods based on PCR. In this context, the aim of this study was to carry out tests on the occurrence of dermatophytes in cattle herds using qPCR methods and a comparative analysis with conventional methods. Each sample collected from ringworm cases and from asymptomatic cattle was divided into three parts and subjected to the real-time PCR technique, direct light microscopy analysis, and culture-based methods. The use of the real-time PCR technique with pan-dermatophyte primers detected the presence of dermatophytes in the sample with a 10.84% (45% vs. 34.17%) higher efficiency than direct analysis with light microscopy. Moreover, a dermatophyte culture was obtained from all samples with a positive qPCR result. In conclusion, it seems that this method can be used with success to detect dermatophytes and monitor cowsheds in ringworm cases and carriers in cattle.

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NESTROFT—A Cost-Effective Mass Screening Tool for the Detection of β-Thalassemia Carrier Status in Anemic Pregnant Women: A Step Toward Reducing the National Disease Burden

Journal of Laboratory Physicians ◽

10.1055/s-0041-1732493 ◽

2021 ◽

Author(s):

Manasi Gosavi ◽

Ramesh Chavan ◽

M. B. Bellad

Keyword(s):

Pregnant Women ◽

Effective Mass ◽

Mass Screening ◽

Predictive Value ◽

Screening Tool ◽

Hematological Parameters ◽

False Negative ◽

Cost Effective ◽

Mean Corpuscular Hemoglobin ◽

Carrier Status

Abstract Introduction β-Thalassemias are inherited hemoglobinopathies commonly encountered in practice. With chances of a promising cure being rare, the prevention of births with this disorder should assume priority, especially in low-resource countries. This can be achieved by the implementation of a mass screening program that is reliable and, at the same time, cost-effective. Objectives This study focuses on the utility of Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) as a mass screening tool to detect thalassemia carriers. Hematological parameters that may predict carrier status were also evaluated. Materials and Methods Hemoglobin estimation was performed on all consented pregnant women. If the patient was found to have hemoglobin < 11 g/dL, the blood sample was subjected to other routine hematological tests along with peripheral smear examination. NESTROFT was performed using 0.36% saline solution. Confirmation was done using high-performance liquid chromatography (HPLC). Statistical Analysis Data obtained were tabulated using version 21 of the Statistical Package for Social Sciences. Means, standard deviations, and percentages were used to describe the sample. Chi-square test and Students’ “t” test were used to identify differences between the groups. Results Of 441 pregnant women enrolled, 206 were found to be anemic. Nineteen (9.2%) of the anemic pregnant women were detected to be carriers of hemoglobinopathies. Among the hematological parameters, mean red blood cell count and reticulocyte count were higher, while mean corpuscular hemoglobin concentration was lower in carriers. Also, carriers were more likely to present with microcytic hypochromic anemia. NESTROFT showed a sensitivity of 84.21%, specificity of 96.25%, a positive predictive value of 69.56%, and a negative predictive value of 98.36%. A false-positive result was seen in 3.74% of the tests, while a false negative result was seen in 15.78% of the tests. Conclusions NESTROFT (0.36%) can be used as a simple and cost-effective mass screening tool for the detection of carrier status. This should be followed by confirmation using HPLC or hemoglobin electrophoresis.

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Five-Year Change in Body Mass Index Predicts Conversion to Mild Cognitive Impairment or Dementia Only in APOE ɛ4 Allele Carriers

Journal of Alzheimer s Disease ◽

10.3233/jad-201360 ◽

2021 ◽

pp. 1-11

Author(s):

Kylie R. Kadey ◽

John L. Woodard ◽

Allison C. Moll ◽

Kristy A. Nielson ◽

J. Carson Smith ◽

...

Keyword(s):

Older Adults ◽

Body Mass Index ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Body Mass ◽

Carrier Status ◽

Healthy Older Adults ◽

E4 Allele ◽

Lifestyle Risk

Background: Body mass index (BMI) has been identified as an important modifiable lifestyle risk factor for dementia, but less is known about how BMI might interact with Apolipoprotein E ɛ4 (APOE ɛ4) carrier status to predict conversion to mild cognitive impairment (MCI) and dementia. Objective: The aim of this study was to investigate the interaction between APOE ɛ4 status and baseline (bBMI) and five-year BMI change (ΔBMI) on conversion to MCI or dementia in initially cognitively healthy older adults. Methods: The associations between bBMI, ΔBMI, APOE ɛ4 status, and conversion to MCI or dementia were investigated among 1,289 cognitively healthy elders from the National Alzheimer’s Coordinating Center (NACC) database. Results: After five years, significantly more carriers (30.6%) converted to MCI or dementia than noncarriers (17.6%), p < 0.001, OR = 2.06. Neither bBMI (OR = 0.99, 95%CI = 0.96–1.02) nor the bBMI by APOE interaction (OR = 1.02, 95%CI = 0.96–1.08) predicted conversion. Although ΔBMI also did not significantly predict conversion (OR = 0.90, 95%CI = 0.78–1.04), the interaction between ΔBMI and carrier status was significant (OR = 0.72, 95%CI = 0.53–0.98). For carriers only, each one-unit decline in BMI over five years was associated with a 27%increase in the odds of conversion (OR = 0.73, 95%CI = 0.57–0.94). Conclusion: A decline in BMI over five years, but not bBMI, was strongly associated with conversion to MCI or dementia only for APOE ɛ4 carriers. Interventions and behaviors aimed at maintaining body mass may be important for long term cognitive health in older adults at genetic risk for AD.

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Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults

Brain Sciences ◽

10.3390/brainsci11010068 ◽

2021 ◽

Vol 11 (1) ◽

pp. 68

Author(s):

Sara G. Aguilar-Navarro ◽

Itzel I. Gonzalez-Aparicio ◽

José Alberto Avila-Funes ◽

Teresa Juárez-Cedillo ◽

Teresa Tusié-Luna ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Cognitive Impairment ◽

Cardiovascular Risk ◽

Mild Cognitive Impairment ◽

Cardiovascular Risk Factors ◽

Apoe Genotype ◽

Carrier Status ◽

Apoe Ε4 ◽

Increased Risk

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

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Frequency of the delta Phe508 mutation and correlation with XV.2c/KM-19 haplotypes in an American population of cystic fibrosis patients: results of a collaborative study

Clinical Chemistry ◽

10.1093/clinchem/36.10.1741 ◽

1990 ◽

Vol 36 (10) ◽

pp. 1741-1746 ◽

Cited By ~ 10

Author(s):

W E Highsmith ◽

G L Chong ◽

H T Orr ◽

T R Perry ◽

D Schald ◽

...

Keyword(s):

Cystic Fibrosis ◽

Haplotype Analysis ◽

Screening Program ◽

Collaborative Study ◽

Population Based ◽

Carrier Status ◽

Chain Reaction ◽

Polymerase Chain ◽

Phenylalanine Residue ◽

Test Result

Abstract The cystic fibrosis (CF) gene has been recently cloned, and a deletion of 3 basepairs (bp) of DNA was found on most of the CF chromosomes. This deletion leads to the synthesis of a protein that lacks a phenylalanine residue at position 508. Using two polymerase chain reaction protocols to study the frequency of this mutation in a series of 192 CF patients, we found the mutation on 72% of affected chromosomes. We then used this value to calculate the predictive value of a negative test result in a population-based screening program for CF carrier status. Haplotype analysis with the polymorphic markers XV.2c and KM-19 on 239 CF chromosomes revealed that 90.7% of CF chromosomes with the deletion had a single haplotype. This haplotype was also associated with 60.4% of CF chromosomes with unknown mutations. These values can be used to calculate the probability of whether an individual from the general population is a carrier of any CF mutation.

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Poor Adherence to the Screening-Based Strategy of Group B Streptococcus Despite Colonization of Pregnant Women in Greece

Pathogens ◽

10.3390/pathogens10040418 ◽

2021 ◽

Vol 10 (4) ◽

pp. 418

Author(s):

Maria Maroudia Berikopoulou ◽

Aikaterini Pana ◽

Theodota Liakopoulou-Tsitsipi ◽

Nikos F. Vlahos ◽

Vasiliki Papaevangelou ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Pregnant Women ◽

Late Onset ◽

Group B Streptococcus ◽

Culture Collection ◽

Carrier Status ◽

Cross Sectional ◽

Screening Guidelines ◽

Group B

Group B streptococcus (GBS) is a leading cause of serious neonatal infections. Maternal GBS colonization is associated with early- and late-onset neonatal disease (EOD/LOD). In Greece, a screening-based strategy is recommended, in which concurrent vaginal-rectal cultures should be obtained between 36 0/7 and 37 6/7 weeks’ gestation. We sought to examine the level of adherence to the GBS screening guidelines and estimate the prevalence of GBS colonization among pregnant women. Although in Greece the screening-based strategy is followed, we also examined known EOD risk factors and linked them to GBS colonization. A cross-sectional study of 604 women postpartum in three hospitals and maternity clinics was conducted. Following written informed consent, data were collected via a short self-completed questionnaire and review of patients’ records. In 34.6% of the enrolled pregnant women, no culture had been taken. Of the remaining, 12.8% had proper vaginal-rectal sample collections. The overall maternal colonization rate was 9.6%. At least one risk factor for EOD was identified in 12.6% of participants. The presence of risk factors was associated with positive cultures (p = 0.014). The rate of culture collection did not differ between women with or without an EOD risk factor. Adherence to a universal screening of pregnant women with vaginal-rectal cultures was poor. Despite probable underestimation of GBS carrier status, almost 1 in 10 participants were GBS positive during pregnancy. Screening of women with risk factors for EOD should, at least, be prioritized to achieve prevention and prompt intervention of EOD.

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