Laboratory parameters provided by Advia 2120 analyser identify structural haemoglobinopathy carriers and discriminate between Hb S trait and Hb C trait

Velasco-Rodríguez, Diego; González-Fernández, Fernando-Ataúlfo; Muriel, Alfonso; Abalo, Lorena; Sopena, María José Martínez; Villarrubia, Jesús; Ropero, Paloma; Plaza, María Paz; Tenorio, María; Martín, Ana Jiménez; Moreno, Gemma; Nieto, Jorge M.; Fuente-Gonzalo, Félix de la; Fernández-Escribano, Marina; López-Jiménez, Francisco Javier; Cava, Fernando

doi:10.1136/jclinpath-2015-203556

Cited by 5 publications

(8 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Heterozygosity for the common African HBB- rs334 hemoglobin S (p.Glu7Val) or rs33930165 hemoglobin C (p.Glu7Gln) beta-globin structural variants have recently been associated with alterations in various red cell laboratory parameters including lower hemoglobin, MCV, MCH, and RDW, along with higher MCHC, RDW, and HbA1c 17,18,20,78–80 . In TOPMed, we were able to identify at least 10 additional low-frequency or rare variants within the HBB locus independently associated with HGB, RBC, MCV, MCH, MCHC, and/or RDW.…”

Section: Discussionmentioning

confidence: 99%

“…These findings add to the further genotypic-phenotypic complexity and clinical spectrum of G6PD deficiency, which is influenced its sex-linkage and zygosity, residual G6PD variant enzyme activity and stability, genetic background, and environmental exposures70 . associated with alterations in various red cell laboratory parameters including lower hemoglobin, MCV, MCH, and RDW, along with higher MCHC, RDW, and HbA1c17,18,20,[71][72][73] . In TOPMed, we were able to identify at least 10 additional low-frequency or rare variants within the HBB locus independently associated with HGB, RBC, MCV, MCH, MCHC, and/or RDW.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Whole genome sequencing association analysis of quantitative red blood cell phenotypes: the NHLBI TOPMed program

Hu¹,

Stilp²,

McHugh³

et al. 2020

Preprint

View full text Add to dashboard Cite

Whole genome sequencing (WGS), a powerful tool for detecting novel coding and non-coding disease-causing variants, has largely been applied to clinical diagnosis of inherited disorders. Here we leveraged WGS data in up to 62,653 ethnically diverse participants from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program and assessed statistical association of variants with seven red blood cell (RBC) quantitative traits. We discovered 14 single variant-RBC trait associations at 12 genomic loci. Several of the RBC trait-variant associations (RPN1, ELL2, MIDN, HBB, HBA1, PIEZO1, G6PD) were replicated in independent GWAS datasets imputed to the TOPMed reference panel. Most of these newly discovered variants are rare/low frequency, and several are observed disproportionately among non-European Ancestry (African, Hispanic/Latino, or East Asian) populations. We identified a 3bp indel p.Lys2169del (common only in the Ashkenazi Jewish population) of PIEZO1, a gene responsible for the Mendelian red cell disorder hereditary xerocytosis [OMIM 194380], associated with higher MCHC. In stepwise conditional analysis and in gene-based rare variant aggregated association analysis, we identified several of the variants in HBB, HBA1, TMPRSS6, and G6PD that represent the carrier state for known coding, promoter, or splice site loss-of-function variants that cause inherited RBC disorders. Finally, we applied base and nuclease editing to demonstrate that the sentinel variant rs112097551 (nearest gene RPN1) acts through a cis-regulatory element that exerts long-range control of the gene RUVBL1 which is essential for hematopoiesis. Together, these results demonstrate the utility of WGS in ethnically-diverse population-based samples and gene editing for expanding knowledge of the genetic architecture of quantitative hematologic traits and suggest a continuum between complex trait and Mendelian red cell disorders.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Whole genome sequencing association analysis of quantitative red blood cell phenotypes: the NHLBI TOPMed program

Hu¹,

Stilp²,

McHugh³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…In the sickle cell trait, although the osmotic fragility of red blood cells is reduced, i.e., positive OFT test, the MCV tends to be within normal range. [ 5 22 23 ] Moreover, dimorphic red blood cells possessing a mixture of microcytic and normal red blood cells may be seen in the early phase of iron depletion and position treatment of iron deficiency anemia. [ 24 ] The red blood cells in these conditions tend to have normal MCV value while the osmotic fragility is decreased.…”

Section: Discussionmentioning

confidence: 99%

Hemolysis area: A new parameter of erythrocyte osmotic fragility for screening of thalassemia trait

Tatu¹,

Sweatman

2018

J Lab Physicians

View full text Add to dashboard Cite

BACKGROUND: One-tube osmotic fragility test (OFT) is widely used for screening thalassemia traits. Interobserver variation may occur with 0.36% NaCl-based OFT due to the naked eye result reading style. PURPOSE: The purpose of this study was to establish and evaluate the novel numerical OFT-based parameter, so-called hemolysis area (HA), in screening thalassemia traits. MATERIALS AND METHODS: The portable spectrophotometer was invented capable of calculating the HA values. The HA values were then compared among 69, 156, and 19 blood samples having positive, negative, and suspicious 0.36% NaCl-based OFT results, respectively; 109 and 135 blood samples having mean corpuscular volume (MCV) ≤80 fL and >80 fL, respectively; and 138 and 106 blood samples having mean corpuscular hemoglobin (MCH) ≤27 pg and >27 pg, respectively. In addition, the HA values were compared in 166 blood samples having different globin gene genotypes. Finally, the HA cutoff value was determined by receiver operation curve (ROC) analysis. RESULTS: The HA values in samples having positive, suspicious, and negative 0.36% NaCl-based OFT were 33.3 ± 14.4, 42.9 ± 10.5, and 65.3 ± 13.4, respectively; in sample having MCV ≤80 fL and >80 fL were 43.1 ± 19.6 and 63.8 ± 14.5, respectively; and in samples having MCH ≤27 pg and >27 pg were 46.7 ± 20.1 and 64.8 ± 14.2, respectively. The HA values in normal, hemoglobin E, SEA-a thalassemia 1, and β-thalassemia traits were 67.1 ± 12.6, 36.4 ± 13.9, 20.2 ± 4.8, and 18.6 ± 1.1, respectively. All were significantly different. ROC analysis established 52.4 as the HA cutoff that had comparable effectiveness to the conventional screening tests. CONCLUSION: The new HA value was effective and could be an alternative choice for screening thalassemia traits.

show abstract

“…One‐way ANOVA was used for intergroup comparisons of red cell parameters according to the number of α‐genes deleted and iron status. Independent t ‐test was used to compare means to historic controls 4 …”

Section: Figurementioning

confidence: 99%

“…1 The βglobin Glu6Lys substitution decreases HbC solubility, causing sickle cell disease when co-inherited with haemoglobin S. However, HbC trait is asymptomatic and displays normal haemoglobin concentration. While some have reported mean corpuscular volume (MCV) in the lower normal range, [2][3][4] others report microcytosis, [5][6][7] typically attributed to iron deficiency and/or co-inheritance of α-thalassaemia trait, as both are prevalent in this population. It thus remains uncertain whether HbC trait in isolation causes microcytosis.…”

mentioning

confidence: 99%

Microcytosis in patients with haemoglobin C trait: is α‐thalassaemia trait to blame?

et al. 2020

View full text Add to dashboard Cite

Laboratory parameters provided by Advia 2120 analyser identify structural haemoglobinopathy carriers and discriminate between Hb S trait and Hb C trait

Abstract: Structural haemoglobinopathy should be investigated in subjects belonging to ethnic groups with high prevalence of variant Hb and with a score of 3 or 4. Erythrocytes of HbAC subjects are smaller and denser than those of HbAS subjects.

Cited by 5 publications

References 35 publications

Whole genome sequencing association analysis of quantitative red blood cell phenotypes: the NHLBI TOPMed program

Whole genome sequencing association analysis of quantitative red blood cell phenotypes: the NHLBI TOPMed program

Hemolysis area: A new parameter of erythrocyte osmotic fragility for screening of thalassemia trait

Microcytosis in patients with haemoglobin C trait: is α‐thalassaemia trait to blame?

Contact Info

Product

Resources

About