Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 706
Filtrar
1.
Clin Biochem ; 71: 69-71, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31299317

RESUMO

We report two cases of hemoglobin Sendagi in a Romanian family residing in Spain: a four-year-old boy and his mother, who had been previously diagnosed with another type of congenital hemolytic anemia and had undergone splenectomy in her country during childhood. The unstable hemoglobin variant, hemoglobin Sendagi, is characterized by decreased oxygen affinity caused by replacement of one of the critical amino acid residues, phenylalanine beta 42 (CD1) of the beta-chain, with valine in the heme pocket, resulting in methemoglobin formation. As a result of migratory movements in Europe, new disease-causing hemoglobin variants are emerging in our country. Here, capillary electrophoresis enabled the identification of the variant and a molecular study was used to establish an accurate diagnosis.


Assuntos
Eletroforese Capilar/métodos , Hemoglobinas Anormais/metabolismo , Mutação , Adulto , Pré-Escolar , Feminino , Humanos , Masculino
2.
Wien Klin Wochenschr ; 131(15-16): 381-384, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31267164

RESUMO

Healthy human blood contains only a trace amount of methemoglobin (Hb M), less than 1%. In Hb M iron is present in the oxidized ferric state (Fe3+) not in the reduced ferrous form (Fe2+) and this reduces the ability of hemoglobin to bind oxygen. The described rare hemoglobin variant Hb M­Hyde Park (also known as Hb M-Akita) results from the substitution of amino acid tyrosine by histidine at position 93 of the beta-globin chain of hemoglobin. The rare Hb variant Hb M­Hyde Park (Hb M­Akita) is mainly inherited autosomal dominant and causes methemoglobinemia. Due to the low frequency of inherited Hb M variants, the diagnosis is challenging. Here, we here report on a family with Hb M­Hyde Park (Hb M­Akita) whose members demonstrated Hb M > 10%, but were, asymptomatic except for chronic cyanosis. Due to human mobility and migration other hemogobin variants, such as beta-thalassemia minor have spread to Austria . A genetic combination of two different hemoglobin variants may result in severe anemia. Genetic counseling for patients with hemoglobin variants, including Hb M­Hyde Park (Hb M­Akita) and beta-thalassemia minor, is essential.


Assuntos
Hemoglobina M/genética , Metemoglobinemia , Áustria , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Humanos , Metemoglobinemia/sangue , Metemoglobinemia/diagnóstico , Metemoglobinemia/genética , Oxiemoglobinas/metabolismo , Talassemia beta/genética
4.
Hematology ; 24(1): 349-352, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30777489

RESUMO

INTRODUCTION: In sickle cell disease (SCD) patients, among the predictors of survival, HbF levels play a significant role in lowering the morbidity and mortality. Coinheritance of 뫧 thalassemia and hereditary persistence of fetal hemoglobin (HPFH) may contribute to variable HbF levels in SCD patients, thus influencing their clinicopathological profile. Such cases are sparsely documented in the literature and thus, we screened the presence of 뫧 thalassemia and HPFH in 126 cases of SCD with high HbF. MATERIAL AND METHODS: A total 126 SCD individuals with raised HbF levels were the study subject. Capillary zone electrophoresis (CZE) was done for the quantitative assessment of hemoglobin variants. HbSC, HbSD, HbAS and HbSE cases were excluded. Asian Indian Gγ(Aγδß)0-thal, δß0-thal (Sicilian, 13.4 kb), (Chinese, 100 kb), HPFH-1 (Black, 106 kb), HPFH-2 (Ghanaian, 105 kb), HPFH-3 (Indian, 48.5 kb) were done by GAP-PCR. RESULTS: Out of 126, 78 cases (62%) were homozygous for SCD. The remaining 48 cases suspected to be heterozygous were furthered screened and 6/48 cases (12.5%) were found to be compound heterozygous. Out of these 6 cases,4(66.66%) had HbS/ δß- Gγ(Aγδß)0 and 2(33%) had HbS/HPFH compound heterozygous condition. None of the patients had δß0-thal (Sicilian, 13.4 kb), (Chinese, 100 kb), HPFH-1 (Black, 106 kb), HPFH-2 (Ghanaian, 105 kb). CONCLUSION: This study highlights the importance of understanding the complex patho-physiology of compound heterozygous cases of HbS/HPFH and HbS/뫧 thalassemia, as these infrequent conditions lead to change in phenotype and clinical severity of the disease. Insight into more such cases will open the window to better analyze the disease pathogenesis in these rare compound heterozygous conditions, as this will be beneficial to formulate proper management protocol in these patients.


Assuntos
Anemia Falciforme , Hemoglobina Fetal , Hemoglobinas Anormais , Heterozigoto , Talassemia beta , Talassemia delta , Adolescente , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/genética , Criança , Feminino , Hemoglobina Fetal/genética , Hemoglobina Fetal/metabolismo , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Humanos , Índia , Masculino , Talassemia beta/sangue , Talassemia beta/genética , Talassemia delta/sangue , Talassemia delta/genética
5.
Hemoglobin ; 43(1): 50-51, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30700173

RESUMO

We report two members of a French family who are carriers of a rare hemoglobin (Hb) variant leading to erythrocytosis: Hb Saint Nazaire [ß103(G5)Phe→Ile; HBB: c.310T>A]. The proband is a 38-year-old woman referred to our institution for a moderate but persistent polycythemia without any clinical consequence. As her mother had a similar blood count, a diagnosis of a Hb variant with high oxygen affinity was proposed. The variant was difficult to detect by capillary electrophoresis (CE) and not distinguishable by high performance liquid chromatography (HPLC) and isoelectric focusing. Finally, a heterozygous mutation on the HBB gene corresponding to Hb Saint Nazaire was identified. This case report illustrates that this rare cause of erythrocytosis can be easily under or misdiagnosed unless several Hb separation techniques are used.


Assuntos
Alelos , Substituição de Aminoácidos , Hemoglobinas Anormais/genética , Mutação , Policitemia/sangue , Policitemia/genética , Adulto , Criança , Análise Mutacional de DNA , Índices de Eritrócitos , Família , França , Hemoglobinas Anormais/metabolismo , Heterozigoto , Humanos
6.
Hematology Am Soc Hematol Educ Program ; 2018(1): 353-360, 2018 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-30504332

RESUMO

The α-thalassemia trait, associated with deletions removing both α-globin genes from 1 chromosome (genotype ζ αα/ζ--), is common throughout Southeast Asia. Consequently, many pregnancies in couples of Southeast Asian origin carry a 1 in 4 risk of producing a fetus inheriting no functional α-globin genes (ζ--/ζ--), leading to hemoglobin (Hb) Bart's hydrops fetalis syndrome (BHFS). Expression of the embryonic α-globin genes (ζ-globin) is normally limited to the early stages of primitive erythropoiesis, and so when the ζ-globin genes are silenced, at ∼6 weeks of gestation, there should be no α-like globin chains to pair with the fetal γ-globin chains of Hb, which consequently form nonfunctional tetramers (γ4) known as Hb Bart's. When deletions leave the ζ-globin gene intact, a low level of ζ-globin gene expression continues in definitive erythroid cells, producing small amounts of Hb Portland (ζ2γ2), a functional form of Hb that allows the fetus to survive up to the second or third trimester. Untreated, all affected individuals die at these stages of development. Prevention is therefore of paramount importance. With improvements in early diagnosis, intrauterine transfusion, and advanced perinatal care, there are now a small number of individuals with BHFS who have survived, with variable outcomes. A deeper understanding of the mechanism underlying the switch from ζ- to α-globin expression could enable persistence or reactivation of embryonic globin synthesis in definitive cells, thereby providing new therapeutic options for such patients.


Assuntos
Transfusão de Sangue Intrauterina , Hemoglobinas Anormais , Hidropisia Fetal , Assistência Perinatal/métodos , Talassemia alfa , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Humanos , Hidropisia Fetal/diagnóstico , Hidropisia Fetal/genética , Hidropisia Fetal/metabolismo , Hidropisia Fetal/terapia , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia alfa/metabolismo , Talassemia alfa/terapia
8.
ACS Sens ; 3(10): 2138-2144, 2018 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-30204417

RESUMO

A new detection system for the endogenous gaseous transmitter and environmental pollutant hydrogen sulfide is presented. It is based on the modulation of the fluorescence spectrum of a coumarin dye by the absorption spectrum of the recombinant hemoglobin I from clam Lucina pectinata upon coordination of the analyte. While we establish that the reported affinity of rHbI for H2S has been overestimated, the association of the protein with an appropriate fluorophore allows fast, easy, and reversible detection and quantification of hydrogen sulfide in buffer as well as biological fluids such as human plasma, with a quantification limit around 200 nM at pH 7.4.


Assuntos
Técnicas Biossensoriais/métodos , Bivalves/metabolismo , Hemoglobinas Anormais/química , Sulfeto de Hidrogênio/análise , Animais , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Humanos , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/química , Concentração de Íons de Hidrogênio , Cinética , Limite de Detecção , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação
9.
Arch Biochem Biophys ; 637: 73-78, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29199120

RESUMO

Human hemoglobin (Hb) Coimbra (ßAsp99Glu) is one of the seven ßAsp99 Hb variants described to date. All ßAsp99 substitutions result in increased affinity for O2 and decreased heme-heme cooperativity and their carriers are clinically characterized by erythrocytocis, caused by tissue hypoxia. Since ßAsp99 plays an important role in the allosteric α1ß2 interface and the mutation in Hb Coimbra only represents the insertion of a CH2 group in this interface, the present study of Hb Coimbra is important for a better understanding of the global impact of small modifications in this allosteric interface. We carried out functional, kinetic and dynamic characterization of this hemoglobin, focusing on the interpretation of these results in the context of a growth of the position 99 side chain length in the α1ß2 interface. Oxygen affinity was evaluated by measuring p50 values in distinct pHs (Bohr effect), and the heme-heme cooperativity was analyzed by determining the Hill coefficient (n), in addition to the effect of the allosteric effectors inositol hexaphosphate (IHP) and 2,3-bisphosphoglyceric acid (2,3-BPG). Computer simulations revealed a stabilization of the R state in the Coimbra variant with respect to the wild type, and consistently, the T-to-R quaternary transition was observed on the nanosecond time scale of classical molecular dynamics simulations.


Assuntos
Hemoglobinas Anormais/química , Hemoglobinas Anormais/metabolismo , 2,3-Difosfoglicerato/farmacologia , Regulação Alostérica , Heme/metabolismo , Hemoglobinas Anormais/genética , Humanos , Técnicas In Vitro , Cinética , Modelos Moleculares , Simulação de Dinâmica Molecular , Oxigênio/metabolismo , Ácido Fítico/farmacologia , Domínios e Motivos de Interação entre Proteínas , Estrutura Quaternária de Proteína
10.
Hemoglobin ; 41(4-6): 308-310, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29219637

RESUMO

Previous molecular analyses of α-thalassemia (α-thal) in the Republic of Macedonia have identified the following genetic defects: -α3.7 (rightward), -(α)20.5 and - -MED I deletions and Hb Icaria [α142, Term→Lys (α2), HBA2: c.427T>A] and polyadenylation signal (polyA) [AATAAA>AATGAA (α2), HBA2: c.*92A>G] point mutations. Here, we report two unrelated patients from the Romani population in the Republic of Macedonia, homozygotes for the α2-globin gene variant Hb Agrinio [α29(B10)Leu→Pro; HBA2: c.89T>C]. To date, Hb Agrinio has been described only in individuals of Greek, Cypriot and Spanish origin. Both of our patients had early presentation of the disease (3.5 years and 2 months, respectively) with frequent blood transfusions from early infancy. They have a severe intermediate phenotype of thalassemia (Hb H disease) with hemoglobin (Hb) levels of 7.8 and 7.7 g/dL, respectively. Although the HBA2: c.89T>C mutation results in an α+ allele, the severe phenotype of the homozygotes is due to the production of hyperunstable α chains that undergo post translational precipitation. This leads to a greater degree of red cell damage and hemolytic anemia. The detection of Hb Agrinio in two unrelated families of Romani ethnic origin, may suggest it is a founder mutation in this population living in the Republic of Macedonia. Considering the severity of the clinical presentation of the homozygotes or compound heterozygotes for this rare Hb variant, a targeted molecular screening for Hb Agrinio mutation carriers should be considered in all patients of Romani ethnic origin with manifested microcytosis.


Assuntos
Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Homozigoto , Talassemia alfa/sangue , Talassemia alfa/genética , Criança , Pré-Escolar , Feminino , Humanos
11.
Hemoglobin ; 41(4-6): 283-285, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29043885

RESUMO

We report a novel HBB: c.114G>C mutation in a Chinese family. This mutation resulted in a ß37(C3)Trp→Cys amino acid substitution and was synonymous with Hb Kent, a hemoglobin (Hb) variant that was reported exclusively in patients of European descent. Though Hb Kent has a normal oxygen affinity and molecular stability, it has a characteristic dual variant appearance on cellulose acetate electrophoresis (CAE) and high performance liquid chromatography (HPLC) caused by the posttranslational modification of cysteine. We also report the phenotypic expression of this variant when coinherited with the Southeast Asian (- -SEA) double α-globin gene deletion.


Assuntos
Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Adulto , Substituição de Aminoácidos , Grupo com Ancestrais do Continente Asiático , China , Família , Feminino , Hemoglobinas Anormais/metabolismo , Humanos , Masculino
12.
Biochemistry ; 56(46): 6125-6136, 2017 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-29064674

RESUMO

Following a previous detailed investigation of the ß subunit of α2ß2 human adult hemoglobin (Hb A), this study focuses on the α subunit by using three natural valency hybrid α(Fe2+-deoxy/O2)ß(Fe3+) hemoglobin M (Hb M) in which O2 cannot bind to the ß subunit: Hb M Hyde Park (ß92His → Tyr), Hb M Saskatoon (ß63His → Tyr), and Hb M Milwaukee (ß67Val → Glu). In contrast with the ß subunit that exhibited a clear correlation between O2 affinity and Fe2+-His stretching frequencies, the Fe2+-His stretching mode of the α subunit gave two Raman bands only in the T quaternary structure. This means the presence of two tertiary structures in α subunits of the α2ß2 tetramer with T structure, and the two structures seemed to be nondynamical as judged from terahertz absorption spectra in the 5-30 cm-1 region of Hb M Milwaukee, α(Fe2+-deoxy)ß(Fe3+). This kind of heterogeneity of α subunits was noticed in the reported spectra of a metal hybrid Hb A like α(Fe2+-deoxy)ß(Co2+) and, therefore, seems to be universal among α subunits of Hb A. Unexpectedly, the two Fe-His frequencies were hardly changed with a large alteration of O2 affinity by pH change, suggesting no correlation of frequency with O2 affinity for the α subunit. Instead, a new Fe2+-His band corresponding to the R quaternary structure appeared at a higher frequency and was intensified as the O2 affinity increased. The high-frequency counterpart was also observed for a partially O2-bound form, α(Fe2+-deoxy)α(Fe2+-O2)ß(Fe3+)ß(Fe3+), of the present Hb M, consistent with our previous finding that binding of O2 to one α subunit of T structure α2ß2 tetramer changes the other α subunit to the R structure.


Assuntos
Hemoglobina M/química , Subunidades de Hemoglobina/química , Hemoglobinas Anormais/química , Oxigênio/metabolismo , Hemoglobina M/metabolismo , Subunidades de Hemoglobina/metabolismo , Hemoglobinas Anormais/metabolismo , Humanos , Modelos Moleculares , Ressonância Magnética Nuclear Biomolecular , Multimerização Proteica , Análise Espectral Raman , Espectroscopia Terahertz
13.
Ann Clin Lab Sci ; 47(5): 625-627, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29066493

RESUMO

We report a case of an extremely rare hemoglobin (Hb) variant-Hb Broomhill, which has been only reported once in the literature. Hemoglobin fractions were determined by capillary electrophoresis (Sebia Capillarys 2 Flex piercing) and high performance liquid chromatography (HPLC) (Bio-Rad Variant™ II Hemoglobin Testing System), respectively. Complete blood count and DNA sequencing were also performed. The capillary electrophoregram revealed a tiny shoulder peak before the HbA peak and a subtle abnormal HbA2 peak (slightly wider and lower), even though the percentage of each hemoglobin fraction was within the reference range (HbA, 97.4%; HbA2, 2.6%). On HPLC, not only the percentage but also the peak shape of each hemoglobin fraction was normal (HbA 88.2%, HbA2 2.5%, HbF 0.6%). Eventually, sequencing analysis of α genes confirmed a missense mutation (CCC>GCC at codon 114 in alpha1 gene) which caused Hb Broomhill variant. Our report suggest that capillary electrophoresis may be an accurate tool for screening and diagnosis of Hb disorders.


Assuntos
Hemoglobina A/genética , Hemoglobinopatias/diagnóstico , Hemoglobinas Anormais/genética , Mutação de Sentido Incorreto , Adulto , Anemia/etiologia , Contagem de Células Sanguíneas , China , Análise Mutacional de DNA , Eletroforese Capilar , Feminino , Hemoglobina A/química , Hemoglobina A/isolamento & purificação , Hemoglobina A/metabolismo , Hemoglobinopatias/sangue , Hemoglobinopatias/genética , Hemoglobinopatias/fisiopatologia , Hemoglobinas Anormais/química , Hemoglobinas Anormais/isolamento & purificação , Hemoglobinas Anormais/metabolismo , Humanos
15.
J Phys Chem B ; 121(37): 8706-8718, 2017 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-28835102

RESUMO

Many globins convert •NO to innocuous NO3- through their nitric oxide dioxygenase (NOD) activity. Mycobacterium tuberculosis fights the oxidative and nitrosative stress imposed by its host (the toxic effects of O2•- and •NO species and their OONO- and •NO2 derivatives) through the action of truncated hemoglobin N (trHbN), which catalyzes the NOD reaction with one of the highest rates among globins. The general NOD mechanism comprises the following steps: binding of O2 to the heme, diffusion of •NO into the heme pocket and formation of peroxynitrite (OONO-), isomerization of OONO-, and release of NO3-. Using quantum mechanics/molecular mechanics free-energy calculations, we show that the NOD reaction in trHbN follows a mechanism in which heme-bound OONO- undergoes homolytic cleavage to give FeIV═O2- and the •NO2 radical but that these potentially harmful intermediates are short-lived and caged by the heme pocket residues. In particular, the simulations show that Tyr33(B10) side chain is shielded from FeIV═O2- and •NO2 (and protected from irreversible oxidation and nitration) by forming stable hydrogen bonds with Gln58(E11) side chain and Leu54(E7) backbone. Aromatic residues Phe46(CD1), Phe32(B9), and Tyr33(B10) promote NO3- dissociation via C-H···O bonding and provide stabilizing interactions for the anion along its egress route.


Assuntos
Hemoglobinas Anormais/metabolismo , Mycobacterium tuberculosis/química , Oxigenases/metabolismo , Hemoglobinas Anormais/química , Ligações de Hidrogênio , Simulação de Dinâmica Molecular , Mycobacterium tuberculosis/metabolismo , Oxigenases/química , Teoria Quântica , Termodinâmica
16.
Hemoglobin ; 41(2): 137-139, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28621168

RESUMO

We describe a case with a low oxygen affinity hemoglobin (Hb) variant who presented with cyanosis in the absence of cardiopulmonary disease. The patient, a 27-year-old pregnant female (P1G2), complained of a productive cough and bluish discoloration of the lips that started 3 days prior to seeking attention. She had no previous episodes and has generally been in good health. A positive family history of cyanosis was obtained in one sibling. Systematic examination, notably the cardiorespiratory system, revealed no abnormalities. The arterial Hb oxygen saturation (SpO2) on pulse oximetry was 81.0% and Hb separation studies revealed an Hb variant identified as Hb Rothschild [ß37(C3)Trp→Arg] (HBB: c.[112 T>A or 112 T>C]) by gene sequencing. The amino acid substitution (Trp→Arg) is an important contact point at the α1ß2 interface and favors a T-quaternary state of the Hb tetramer. This leads to a low oxygen affinity state, which results in premature release of oxygen and drop in oxygen saturation. In the absence of cardiopulmonary disease, a decreased oxygen saturation reading, with or without cyanosis, should arouse suspicion for a possible dysHb.


Assuntos
Índices de Eritrócitos , Hemoglobinas Anormais , Oximetria , Complicações Hematológicas na Gravidez , Adulto , Cianose/sangue , Cianose/genética , Feminino , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Humanos , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/genética
17.
A A Case Rep ; 9(7): 197-198, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28542050

RESUMO

A 25-year-old Caucasian man with a history of spherocytosis, splenectomy, recurrent blood transfusion, and no cardiopulmonary disease presented for an emergent laparoscopic cholecystectomy with a baseline pulse oximetric saturation (SpO2) of 88% while breathing room air. The SpO2 increased to only 89% during preoxygenation with an FIO2 1.0. Multiple arterial blood samples revealed SaO2 as high as 100% with PaO2 averaging 390 mm Hg. He was subsequently diagnosed with a dyshemoglobin, hemoglobin Köln. The simultaneous presentation of a stable patient from a cardiopulmonary perspective with normal arterial oxygen tension and saturation in the blood gas analyses despite a low SpO2 measurement outlines the importance of integrating the history of present illness and both the importance and the limitation of the pulse oximetry.


Assuntos
Hemoglobinas Anormais/metabolismo , Hemoglobinas/metabolismo , Oxigênio/sangue , Adulto , Anestesia Geral , Gasometria , Hemoglobinas/química , Hemoglobinas Anormais/química , Humanos , Masculino , Oximetria
18.
Hemoglobin ; 41(1): 1-5, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28532286

RESUMO

We describe an insertion variant on the α1-globin gene (HBA1) identified in a 49-year-old woman of Jurassian ancestry presenting with macrocytosis and erythrocytosis. The variant resulted in a peak of 15.5% of the total hemoglobin (Hb) on high performance liquid chromatography (HPLC). Stability and oxygen affinity testing revealed that the variant was stable and had an increased oxygen affinity. Molecular genetic testing detected the heterozygous sequence variant Hb Bakersfield [α50(CE8)His→0; Arg-Ser-His- inserted between 49(CE7) and 51(CE9) of α1; HBA1: c.151_152insGGAGCC (p.Ser50_His51insArgSer)] in the index patient, one of her sons, as well as in two of her grandchildren, who showed a similar hematological pattern.


Assuntos
Substituição de Aminoácidos , Códon , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Mutagênese Insercional , Oxigênio/metabolismo , alfa-Globinas/genética , alfa-Globinas/metabolismo , Adulto , Pré-Escolar , Análise Mutacional de DNA , Feminino , Hemoglobinas Anormais/química , Heterozigoto , Humanos , Lactente , Cinética , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Conformação Molecular , Linhagem , Ligação Proteica , Adulto Jovem , alfa-Globinas/química , Globinas beta/química , Globinas beta/metabolismo
19.
Biomed Res Int ; 2017: 1261972, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28553644

RESUMO

Hemoglobin (Hb) Lepore is composed of two normal α chains and two 뫧 fusion globins that arise from unequal crossover events between the δ- and ß-globin genes. The Hb Lepore is widespread all over the world and in many ethnic groups. It includes some of the few clinically significant Hb variants that are associated with a ß-thalassemia phenotype. Here, we describe the first occurrence of Hb Lepore Boston Washington in a Syrian individual. The patient, a 10-year-old child, shows severe anemia with a Hb level of 6.85 g/dL and typical thalassemic red cell indices. The diagnostic procedure implies hematological, biochemical, and molecular analysis, including multiplex ligation-dependent probe amplification (MLPA) assay, GAP-PCR, and DNA sequencing. This latter allowed us to define the correct structure of the hybrid δß-globin gene. The knowledge of the spectrum of mutations associated with different geographical areas is the prerequisite to set up large-scale screening programs and be able to offer genetic counseling to couples at risk.


Assuntos
Hemoglobinas Anormais , Homozigoto , Talassemia beta , Criança , Hemoglobinas Anormais/química , Hemoglobinas Anormais/genética , Hemoglobinas Anormais/metabolismo , Humanos , Síria , Talassemia beta/genética , Talassemia beta/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA