Hb Vila Real [β36(C2)Pro→His]: A Newly Discovered High Oxygen Affinity Variant

Bento, Celeste; Ribeiro, M. Letícia; Cunha, Elizabete; Rebelo, Umbelina; Granjo, Elisa; Granado, Claudio; Tamagnini, Gabriele

doi:10.3109/03630260009002275

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…These changes are important for the formation and stability of the Hb A2 variant. A similar decrease has been observed for the Hb Vila Real (HBB g.240C>A) [Bento et al, 2000], due to the same substitution in the b-chain; in fact it was only 36% in the carrier.…”

Section: New Alleles: Molecular Mechanism and Phenotypesupporting

confidence: 52%

Epidemiology of the delta globin alleles in southern Italy shows complex molecular, genetic, and phenotypic features

Angioletti

Lacerra

Gaudiano³

et al. 2002

Hum. Mutat.

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We characterized mutations and haplotypes of the delta-globin gene (HBD, MIM# 142000) in two regions of southern Italy. Mutations were discovered by screening for individuals with Hb A2<2%. In Basilicata, about 10,000 students were screened and 53 carriers in 43 unrelated families were diagnosed; in Campania, cases were referred through a routine thalassemia counseling service. Twelve alleles were detected. Four were novel variants [Hb A2-Metaponto (g.238C>A), Hb A2-Campania (g.302C>A), Hb A2-Lucania (g.393C>G), and Hb A2-Capri (g.443G>T)]. Hb A2-Lucania was not inherited but had arisen in the propositus. Two were novel mutations in the noncoding regions: the substitutions IVS2+6T>A, presumably affecting the splicing, and g.-126A>T in the GATA motif presumably affecting transcription. All novel alleles were found associated with haplotypes common in the Mediterranean area. The remaining six were alleles already described. The Hb A2-Yialousa (g.82G>T) was the most prevalent (42/63 families). Recurrent homologous crossing-over events have, most likely, linked this allele to Haplotypes IX (24 families), IV (10 families), or III (seven families). The ratio of Haplotypes IX:IV:III was about the same in the two regions. The rare allele Hb A2-NYU (g.39T>A) was found in 11 families from Basilicata associated with Haplotype I. All the 11 families lived in a restricted area extending from the Ionian Coast for 15 km along the Angri and Sinni Rivers. A founder effect most probably gave origin to this isolated group. The remaining four alleles were rare: the 7.2-kb deletion Corfù type (HBD g.-5946_1262del), Hb A2-Mitsero (g.14C>T), Hb A2-Etolia (g.385T>C), Hb A2-Coburg (g.1376G>A). Correlation between genotype and phenotype was established in 103 carriers.

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Section: New Alleles: Molecular Mechanism and Phenotypesupporting

confidence: 52%

Epidemiology of the delta globin alleles in southern Italy shows complex molecular, genetic, and phenotypic features

Angioletti

Lacerra

Gaudiano³

et al. 2002

Hum. Mutat.

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“…Cases have been described showing unusual incidences of spontaneous abortion in female carriers caused by the lower oxygenation of the fetus resulting from either the alteration in the physiological O 2 gradient affinity between fetal and maternal blood or by placental infarction caused by the high viscosity of the mother's blood …”

Section: Molecular Etiology and Clinical Manifestationsmentioning

confidence: 99%

Genetic basis of congenital erythrocytosis

Bento

2018

Int J Lab Hematology

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“…In severe symptomatic cases, regular exchange transfusion has to be considered. Cases have been described showing unusual incidences of spontaneous abortion in female carriers caused by the lower oxygenation of the fetus resulting from either the alteration in the physiological oxygen gradient affinity between fetal and maternal blood or by placental infarction caused by the high viscosity of the mother's blood [Koller et al., , Bento et al., ].…”

Section: Clinical Significance Of Mutation Identificationmentioning

confidence: 99%

Genetic Basis of Congenital Erythrocytosis: Mutation Update and Online Databases

et al. 2013

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Congenital Erythrocytosis (CE), also called congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. 3Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and generally results from mutations in the erythropoietin-receptor gene (EPOR).Secondary congenital erythrocytosis arises from conditions which cause tissue hypoxia thus resulting in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (genes HBB, HBA1 and HBA2), decreased production of 2,3-biphosphoglycerate due to mutations in the BPGM gene, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1 and EGLN1). Depending on the affected gene CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo.Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients.With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive internet-based database focusing on the registration of clinical history, hematological, biochemical and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database (LOVD).

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Hb Vila Real [β36(C2)Pro→His]: A Newly Discovered High Oxygen Affinity Variant

Cited by 7 publications

References 15 publications

Epidemiology of the delta globin alleles in southern Italy shows complex molecular, genetic, and phenotypic features

Epidemiology of the delta globin alleles in southern Italy shows complex molecular, genetic, and phenotypic features

Genetic basis of congenital erythrocytosis

Genetic Basis of Congenital Erythrocytosis: Mutation Update and Online Databases

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