Two Alleles with RHCE*nt818C>T Change Encode the Low Prevalence Rh Antigen STEM.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3159-3159 ◽  
Author(s):  
Christine Halter-Hipsky ◽  
Kim Hue-Roye ◽  
Gail Coghlan ◽  
Christine Lomas-Francis ◽  
Marion E. Reid
Keyword(s):  
South African ◽  
Molecular Basis ◽  
Index Case ◽  
Conflicts Of Interest ◽  
Direct Sequencing ◽  
Molecular Testing ◽  
Variable Expression ◽  
New Findings ◽  
Low Prevalence ◽  
Original Index

Abstract Abstract 3159 Poster Board III-96 Background According to the original (and only) report, the low prevalence Rh antigen, STEM, is associated with an altered e phenotype. Approximately 65% of hrS– and 30% of hrB– RBCs from South African donors are STEM+. STEM has a variable expression, which is an inherited characteristic. Anti-STEM has induced mild HDFN (Marais, et al., Transf Med 1993;3:35-41). The purpose of this study was to determine the molecular basis associated with STEM expression. Material and Methods Blood samples and reagents were from our collections. Hemagglutination and DNA extraction were performed by standard methods. Molecular testing included direct sequencing and cloning of cDNA, AS-PCR, PCR-FRLP, and sequencing specific exons of gDNA. Results Three STEM+ samples (including the original index case) had RHCE*ceBI [ce 48C (16C), 712G (238V), 818T (273V), 1132G (378V)] (Noizat-Pirenne, et al., Blood 2002;100:4223-31) and 6 had a new allele, which we name RHCE*ceSM (ce 48C, 712G, 818T). In contrast, 8 STEM– samples (which included hrS– and hrB– samples) did not have the RHCE*818C>T change. RBCs with the ceBI phenotype expressed STEM more strongly than those with the ceSM phenotype. Conclusions The previously reported allele RHCE*ceBI and a new allele, RHCE*ceSM, encode the STEM antigen. This study also revealed other new findings: (i) ceSM encodes a weaker expression of STEM than does ceBI, which explains the previously reported variable expression, (ii) provides an explanation for why not all hrS– and hrB– RBCs express STEM. RBCs with ceAR, ceMO, and ceEK, phenotypes are hrS– STEM–, and RBCs with ceS phenotypes type hrB–, STEM–, (iii) ceBI and ceSM do not express hrS but do express hrB. It is likely that anti-hrS made by hrS– STEM– people (ceAR, ceMO, ceEK) will be incompatible with hrS– STEM+ RBCs, and vice versa. Our findings provide a means to positively identify the STEM+ phenotypes, which, by hemagglutination, is virtually impossible due to the dearth of anti-STEM. Further, it provides a tool to provide suitable antigen-negative RBC products to a patient who has made an ‘e-like’ antibody. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Population-Specific Optimized GeneXpert Pooling Algorithm for Chlamydia trachomatis and Neisseria gonorrhoeae To Reduce Cost of Molecular Sexually Transmitted Infection Screening in Resource-Limited Settings

2020 ◽  
Vol 58 (9) ◽  
Author(s):  
Sarah Connolly ◽  
William Kilembe ◽  
Mubiana Inambao ◽  
Ana-Maria Visoiu ◽  
Tyronza Sharkey ◽  
...  
Keyword(s):  
Trichomonas Vaginalis ◽  
Molecular Testing ◽  
Resource Limited Settings ◽  
Syphilis Infection ◽  
Syndromic Management ◽  
Sexually Transmitted ◽  
Factors Associated ◽  
Resource Limited ◽  
The Cost ◽  
Low Prevalence

ABSTRACT The sexually transmitted infections (STIs) chlamydia (CT) and gonorrhea (NG) are often asymptomatic in women and undetected by syndromic management, leading to complications such as pelvic inflammatory disease, infertility, and ectopic pregnancy. Molecular testing, such as the GeneXpert CT/NG assay, is highly sensitive, but cost restraints preclude implementation of these technologies in resource-limited settings. Pooled testing is one strategy to reduce the cost per sample, but the extent of savings depends on disease prevalence. The current study describes a pooling strategy based on identification of sociodemographic and laboratory factors associated with CT/NG prevalence in a high-risk cohort of Zambian female sex workers and single mothers conducted from 2016 to 2019. Factors associated with testing positive for CT/NG via logistic regression modeling included city, younger age, lower education, long-acting reversible contraception usage, Trichomonas vaginalis infection, bacterial vaginosis, and incident syphilis infection. Based on these factors, the study population was stratified into high-, intermediate-, and low-prevalence subgroups and tested accordingly—individually, pools of 3, or pools of 4, respectively. The cost per sample was reduced from $18 to as low as $9.43 in the low-prevalence subgroup. The checklist tool and pooling approach described can be used in a variety of treatment algorithms to lower the cost per sample and increase access to molecular STI screening. This is particularly valuable in resource-limited settings to detect and treat asymptomatic CT/NG infections missed by traditional syndromic management.

The Molecular Basis of Antithrombin Deficiency in Belgian and Dutch Families

1998 ◽  
Vol 80 (09) ◽  
pp. 376-381 ◽  
Author(s):  
W. Lissens ◽  
S. Seneca ◽  
P. Capel ◽  
B. Chatelain ◽  
P. Meeus ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Gene Deletion ◽  
Direct Sequencing ◽  
Genetic Defect ◽  
Polymorphism Analysis ◽  
Type I ◽  
Type Ii ◽  
Antithrombin Deficiency ◽  
Venous Thromboembolic Events ◽  
At Deficiency

SummaryThe molecular basis of hereditary antithrombin (AT) deficiency has been investigated in ten Belgian and three Dutch unrelated kindreds. Eleven of these families had a quantitative or type I AT deficiency, with a history of major venous thromboembolic events in different affected members. In the other two families a qualitative or type II AT deficiency was occasionally diagnosed.DNA studies of the AT gene were performed, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis, followed by direct sequencing of the seven exons and intronexon junction regions. Six novel point mutations were identified: four missense, one nonsense mutation and a single nucleotide deletion near the reactive site, causing a frameshift with premature translation termination. In two kindreds the underlying genetic defect was caused by a whole gene deletion, known as a rare cause of AT deficiency. In these cases, Southern blot and polymorphism analysis of different parts of the AT gene proved useful for diagnosis. In another kindred a partial gene deletion spanning 698 basepairs could precisely be determined to a part of intron 3B and exon 4. In two type I and in both type II AT deficient families a previously reported mutation was identified. In all cases, the affected individuals were heterozygous for the genetic defect.

scholarly journals Low Prevalence of Liver Disease but Regional Differences in HBV Treatment Characteristics Mark HIV/HBV Co-Infection in a South African HIV Clinical Trial

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e74900 ◽  
Author(s):  
Prudence Ive ◽  
William MacLeod ◽  
Nompumelelo Mkumla ◽  
Catherine Orrell ◽  
Ute Jentsch ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Liver Disease ◽  
South African ◽  
Regional Differences ◽  
Treatment Characteristics ◽  
Low Prevalence

scholarly journals Cystic fibrosis gene mutations and polymorphisms in Saudi men with infertility

2020 ◽  
Vol 40 (4) ◽  
pp. 321-329
Author(s):  
Talal AlMaghamsi ◽  
Naeem Iqbal ◽  
Nabil Abdullrahman Al-Esaei ◽  
Muhsina Mohammed ◽  
Kamel Zein Eddin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Sample Size ◽  
Conflicts Of Interest ◽  
Direct Sequencing ◽  
Tertiary Care ◽  
Gene Mutations ◽  
Small Sample ◽  
Cystic Fibrosis Gene ◽  
Control Group ◽  
Primary Infertility

ABSTRACT BACKGROUND: Some mutations of the cystic fibrosis transmembrane regulator ( CFTR ) gene may impair spermatogenesis or cause a congenital absence of the vas deferens that manifests as isolated male infertility. OBJECTIVE: Assess the frequency and analyze the spectrum of CFTR gene variations in Saudi men with primary infertility. DESIGN: Prospective, cross-sectional. SETTING: Tertiary care specialist hospital in Jeddah. PATIENTS AND METHODS: Genomic DNA was extracted from peripheral blood samples of Saudi men who presented with primary infertility to the outpatient andrology clinic with either azoospermia or oligoasthenoteratozoospermia. Polymerase chain reaction and direct sequencing were used to identify all variants of the CFTR gene. MAIN OUTCOME MEASURES: Proportion of the patients with a mutant CFTR gene and the spectrum of CFTR gene variations. SAMPLE SIZE: 50 infertile Saudi men. RESULTS: This study identified 10 CFTR gene variants in 7 (14%) subjects (100 chromosomes). The detected variants and polymorphisms were: c.1408G>A, c.4389G>A, c.2562T>G, c.869+11C>T, c.2909-92G>A, c.3469-65C>A, c.1210-6delT, c.1210-6T>A, c.2988+1G>A, and c.1210-13GT>TG. CONCLUSION: We demonstrated that 14% of the study subjects had one or more CFTR mutations and these were compounded in most of the affected patients. The spectrum of CFTR gene mutations in these subjects was similar to the mutations reported in other studies throughout the world. LIMITATIONS: Small sample size and the lack of a control group. CONFLICTS OF INTEREST: None.

scholarly journals Collective action problems and the role of South African business in national and regional accords

1997 ◽  
Vol 28 (3) ◽  
pp. 105-112 ◽  
Author(s):  
Nicoli Nattrass
Keyword(s):  
Collective Action ◽  
South African ◽  
Conflicts Of Interest ◽  
Local Development ◽  
National Level ◽  
Eastern Cape ◽  
Business Organizations ◽  
Collective Action Problems ◽  
Incomes Policy

This article examines some of the collective action problems which beset South African business in national and regional accords. The first part concludes that incomes policy type accords at national level are unlikely to be successful in South Africa. The main part of the article considers accords at subnational level where conflicts of interest are more easily (but not entirely) resolved. This is done by means of two case studies of business acting collectively to promote regional or local development. The first looks at the role of organized business in the Eastern Cape Socio-Economic Consultative Council (ECSECC). It is suggested that the geographical divide between the various business organizations undermines the potential for collective action. The second describes the more successful local housing accord which was negotiated in Port Elizabeth.

Natalignathus, gen. nov. and larvae of Atanygnathus: a missing phylogenetic link between subtribes Quediina and Tanygnathinina (Coleoptera:Staphylinidae:Staphylininae:Staphylinini)

2005 ◽  
Vol 19 (1) ◽  
pp. 75 ◽  
Author(s):  
A. Yu. Solodovnikov
Keyword(s):  
Comparative Study ◽  
South African ◽  
Unknown Function ◽  
Phylogenetic Relationships ◽  
New Genus ◽  
New South ◽  
Head Capsule ◽  
Rove Beetle ◽  
New Findings ◽  
Shed Light

Discovery of adults and a larva of Natalignathus, a new South African endemic genus, and examination of previously undescribed larvae of Atanygnathus Jakobson shed light on the phylogenetic relationships of the puzzling rove beetle subtribe Tanygnathinina (Staphylinidae : Staphylininae : Staphylinini). Based on plesiomorphic states for many characters of Natalignathus, gen. nov., inferred on the basis of comparison of the new genus with Atanygnathus, various Quediina and other Staphylinini, Natalignathus can be considered either a relatively plesiomorphy-rich member of Tanygnathinina, or a derived genus of Quediina, essentially linking these two subtribes together. Based on morphological and distributional data, it is preliminarily assumed that Atanygnathus evolved from some lineage of southern Quediina, which currently are very poorly known. Comparative study of the adults of Natalignathus and Atanygnathus allows correction of earlier misinterpretations of the structure of the aedeagus and head capsule ridges of Atanygnathus. Detailed morphological descriptions are provided for adults and a larva of Natalignathus and for the larvae of two species of Atanygnathus, A. bicolor (Casey) and A. sp. 1. Special appendages of unknown function are present on the mesothoracic spiracles of the examined larvae of Atanygnathus. No similar structures are known in any other group of Staphylinidae or Coleoptera. Based on the new findings, a review of the state of knowledge of the subtribes Quediina and Tanygnathinina and an updated diagnosis of the latter are provided.

scholarly journals Molecular basis for antithrombin III type I deficiency: three novel mutations located in exon IV

Blood ◽  
1991 ◽  
Vol 78 (9) ◽  
pp. 2305-2309 ◽  
Author(s):  
D Vidaud ◽  
J Emmerich ◽  
ME Sirieix ◽  
P Sie ◽  
M Alhenc-Gelas ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Antithrombin Iii ◽  
Polymerase Chain Reaction Amplification ◽  
Direct Sequencing ◽  
Thrombotic Complication ◽  
Type I ◽  
Missense Mutations ◽  
Functional Protein ◽  
Molecular Abnormalities ◽  
At Iii

Abstract Antithrombin III (AT III) type I deficiencies are characterized by a 50% decrease of both immunoreactive and functional protein and carry a high risk of thrombotic complication. We have studied the molecular basis for such deficiencies by asymmetric polymerase chain reaction amplification and direct sequencing of the seven exons and of the intron-exon junction of the AT III gene. Three different mutations were observed in the exon IV: a 4-bp deletion, a 2-bp deletion, and a nucleotide insertion. Each of these mutations results in a frameshift introducing premature stop codons at positions 313, 309, and 232, respectively. These results were confirmed by dot-blot analysis with allele-specific oligonucleotide probes. Furthermore, no mutation was observed in the other six exons. The comparison of the type of mutations observed by our group in six cases of type I deficiencies and in 16 cases of type II heparin binding site variants deficiencies suggests that the former are caused by heterogeneous molecular abnormalities while the latter are caused by recurrent missense mutations.

scholarly journals An Observational Pilot Study Evaluating the Utility of Minimally Invasive Tissue Sampling to Determine the Cause of Stillbirths in South African Women

2019 ◽  
Vol 69 (Supplement_4) ◽  
pp. S342-S350 ◽  
Author(s):  
Shabir A Madhi ◽  
Jayani Pathirana ◽  
Vicky Baillie ◽  
Clare Cutland ◽  
Yasmin Adam ◽  
...  
Keyword(s):  
Pilot Study ◽  
Minimally Invasive ◽  
South African ◽  
Fluid Collection ◽  
African Women ◽  
World Health ◽  
Molecular Testing ◽  
Microbial Culture ◽  
Tissue Sampling ◽  
Biological Investigation

Abstract Background Despite approximately 2.6 million stillbirths occurring annually, there is a paucity of systematic biological investigation and consequently knowledge on the causes of these deaths in low- and middle-income countries (LMICs). We investigated the utility of minimally invasive tissue sampling (MITS), placental examination, and clinical history, in attributing the causes of stillbirth in a South African LMIC setting. Methods This prospective, observational pilot study undertook sampling of brain, lung, and liver tissue using core biopsy needles, blood and cerebrospinal fluid collection, and placental examination. Testing included microbial culture and/or molecular testing and tissue histological examination. The cause of death was determined for each case by an international panel of medical specialists and categorized using the World Health Organization’s International Classification of Diseases, Tenth Revision application to perinatal deaths. Results A cause of stillbirth was identifiable for 117 of 129 (90.7%) stillbirths, including an underlying maternal cause in 63.4% (n = 83) and an immediate fetal cause in 79.1% (n = 102) of cases. The leading underlying causes of stillbirth were maternal hypertensive disorders (16.3%), placental separation and hemorrhage (14.0%), and chorioamnionitis (10.9%). The leading immediate causes of fetal death were antepartum hypoxia (35.7%) and fetal infection (37.2%), including due to Escherichia coli (16.3%), Enterococcus species (3.9%), and group B Streptococcus (3.1%). Conclusions In this pilot, proof-of-concept study, focused investigation of stillbirth provided granular detail on the causes thereof in an LMIC setting, including provisionally highlighting the largely underrecognized role of fetal sepsis as a dominant cause.

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