RESUMEN
Hb J-Paris-I [HBA2: c.38C>A (or HBA1)] is a stable fast-moving hemoglobin (Hb) that elutes in the P3 window on high performance liquid chromatography (HPLC). The mutation can happen on either the α1- or α2-globin gene. Codon 12 changes from GCC to GAC to replace the alanine amino acid with aspartic acid. This change is external with no clinical significance. The elution in the P3 wave on HPLC can interfere with the glycated Hb assay by HPLC. In this study, data of 11 cases of Hb J-Paris-I were thoroughly presented. The majority of the cases were of Indian ethnicity. The mean value of Hb J-Paris-I on HPLC was 26.7 ± 2.0%. The retention time (RT) was 1.75 ± 0.03 min. The isoelectric focusing (IEF) mean value was -5.6 (range -6.1 to -4.9). Hb A2 was consistently reduced to 1.8 ± 0.3%. A fraction of 0.8% corresponding to the Hb A2-J-Paris-I (α2J-Paris-Iδ2) is likely to be concealed within the A0 peak of Hb A on HPLC. Interestingly, two cases were associated with two different polymorphisms [HBA2: c.-24C>G or Cap +14 (C>G) and HBA2: c.*136A>G polymorphism] without apparent effect on the variant expression.
Asunto(s)
Hemoglobinopatías , Hemoglobinas Anormales , Talasemia alfa , Cromatografía Líquida de Alta Presión , Genotipo , Hemoglobina Glucada/genética , Hemoglobina A2/genética , Hemoglobina J , Hemoglobinopatías/genética , Hemoglobinas Anormales/genética , Humanos , Globinas alfa/genética , Talasemia alfa/genéticaRESUMEN
Hb Winnipeg [α75(EF4)AspâTyr (α2); HBA2: c.226G>T (or HBA1)] is a stable α-globin chain variant described in a few articles. The majority of reported cases in older articles were clustered in Canada. It can occur on both α1- and α2-globin genes and in different populations. In this study, eight cases of Hb Winnipeg were characterized by DNA sequencing during a wide-spectrum study of suspected α-globin gene variants collected in the United Kingdom. All cases detected peaked in the S window between 4.4 and 4.54 min. on high performance liquid chromatography (HPLC). The isoelectric focusing (IEF) averaged at 6.21 below Hb A. All the mutations were detected on the α1-globin gene except in one case. The ethnic origin of the majority of the patients was Canadian. Only one case was associated with the common polymorphism HBA2: c.-24C>G (or HBA1) [Cap +14 (C>G)] on both α-globin genes without any apparent effect on the variant expression. All cases were detected in a heterozygous state. Hb Winnipeg expression was consistently lower than the theoretical value for α chain variants, ranging between 11.8 and 15.8% of total hemoglobin (Hb). This study gave more details about Hb Winnipeg that may help in presumptive diagnosis, especially in routine laboratories.
Asunto(s)
Hemoglobinas Anormales , Talasemia alfa , Anciano , Canadá , Genotipo , Hemoglobina Glucada/genética , Hemoglobinas Anormales/genética , Humanos , Mutación , Globinas alfa/genética , Talasemia alfa/genéticaRESUMEN
Hb Manitoba [α102(G9)SerâArg] is a rare α chain variant with diverse ethnic origins. It is mildly unstable with an expression of around 10.0-14.2% in the heterozygous state in most literature. In this study, 12 cases of Hb Manitoba [11 cases carried Hb Manitoba II (HBA1: c.309C>A) and one case carried Hb Manitoba IV (HBA1: c.307A>C)] were detected during a wide-spectrum study of α chain variants in the UK. Fluctuation in variant expression from 6.9 to 15.2% of total Hb on high performance liquid chromatography (HPLC) would pose a diagnostic dilemma in routine laboratories. Focusing on the variant expression, the median of Hb Manitoba was around 11.5% of total Hb in three cases, apparently with normal hemoglobin (Hb), and normal red blood cell (RBC) indices. Two cases showed a higher expression (13.9 and 15.2%) and five cases showed a lower expression (6.9-9.9%). The common α-thalassemia (α-thal) -α3.7 (rightward) deletion coexisted with one case of increased Hb Manitoba expression. Iron (or other nutrient) deficiency was likely the cause of decreased Hb Manitoba percentage in this study. The α73(EF2)ValâVal (α2) (HBA2: c.222G>T) polymorphism is published for the first time and coexisted with two cases. The Cap +14 (C>G) (HBA2: c.-24C>G) polymorphism coexisted with another case in a heterozygous state. In conclusion, the fluctuation in variant expression can cause a diagnostic dilemma, especially in routine laboratories. Screening for the common -α3.7 deletion and iron deficiency is recommended when an α chain variant is suspected.
Asunto(s)
Sustitución de Aminoácidos , Codón , Hemoglobinas Anormales/genética , Mutación , Globinas alfa/genética , Talasemia alfa/genética , Adulto , Alelos , Análisis Mutacional de ADN , Índices de Eritrocitos , Femenino , Regulación de la Expresión Génica , Genotipo , Humanos , Masculino , Análisis de Secuencia de ADN , Talasemia alfa/sangre , Talasemia alfa/diagnósticoRESUMEN
Hb J-Meerut [HBA2: c.362C>A (or HBA1)] is a rare, stable, nonpathogenic α-globin gene variant that peaks in the area between the P3 and A0 windows on high performance liquid chromatography (HPLC). Few cases from different ethnic origins have been published but the majority were Asian Indians. Coinheritance with other hemoglobin (Hb) variants are rarer and can change the Hb J-Meerut phenotype making a diagnostic dilemma. In this study, we have reported 15 cases of Hb J-Meerut, discovered during a wide spectrum study of α-globin chain variants in the UK. The diagnosis was confirmed by forward and reverse DNA sequencing of the α1- and α2-globin genes. The average of the Hb J-Meerut expression was 20.9% of total Hb and characterized by a retention time (RT) of 1.9 min. (on average) on HPLC. The median of isoelectric focusing (IEF) was 5.6 mm above Hb A. Among the 15 cases studied, one case coinherited the Hb E (HBB: c.79G>A) mutation in heterozygosity and another case was associated with the Cap +14 (C>G) [HBA1: c.-24C>G (or HBA2)] variant. We noticed that the coinheritance of the Hb E mutation reduced the Hb J-Meerut expression with the formation of a hybrid peak missed on the HPLC chromatograph. We also noticed an increased expression of Hb J-Meerut in the case showing the coinheritance of the HBA2: c.-24C>G (or HBA1) variant.
Asunto(s)
Alelos , Genotipo , Hemoglobina J/genética , Globinas alfa/genética , Cromatografía Líquida de Alta Presión , Hemoglobinas Anormales/genética , Heterocigoto , Humanos , Mutación , Regiones Promotoras Genéticas , Talasemia alfa/diagnóstico , Talasemia alfa/genéticaRESUMEN
Over many years, cases of suspected α-globin chain variants were collected from different parts of the UK. The suspicion was based on the clinical picture, high performance liquid chromatography (HPLC) variant percentage, retention time (RT) and isoelectric focusing (IEF). DNA sequencing and the restriction enzyme EaeI were used for definitive diagnosis. One hundred and forty-eight variants were confirmed on one or both of the two α-globin genes (HBA2, HBA1). These cases were identified as 46 different α-globin chain variants. The most common variants were Hb J-Meerut [HBA2: c.362C>A (or HBA1)] (10.1%) and Hb Q-India (HBA1: c.193G>C) (8.1%), followed by Hb J-Paris-I [HBA2: c.38C>A (or HBA1)] and Hb Manitoba II (HBA1: c.309C>A) (7.4% for each). Other α variants were detected at lower frequencies. Two novel alleles were also detected: Hb Walsgrave [α116(GH4)GluâVal (HBA2: c.350A>T)] and Hb Coombe Park [α127(H10)LysâGlu (HBA2: c.382A>G)]. The majority of the ethnic origin was Indian. The positive predictive value for α variant identification by HPLC-RT analysis was 65.9%, 41.9% by IEF, and using both RT and IEF, the value was 72.1%. The number of variants was higher in HBA1 than in HBA2 genes and in exons 1 and 2 than in exon 3. There was no clustering of mutations in consecutive codons. This study, the characterization of a wide spectrum of α-globin chain variants, can facilitate the presumptive diagnosis of these variants prior to screening by a panel of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), and a definitive diagnosis by DNA sequencing.
Asunto(s)
Variación Genética , Globinas alfa/genética , Talasemia alfa/epidemiología , Talasemia alfa/genética , Alelos , Codón , Índices de Eritrocitos , Exones , Frecuencia de los Genes , Genotipo , Hemoglobinopatías/epidemiología , Hemoglobinopatías/genética , Humanos , Mutación , Vigilancia de la Población , Reino Unido/epidemiología , Reino Unido/etnología , Talasemia alfa/sangre , Talasemia alfa/diagnósticoRESUMEN
We review and report here the genotypes and phenotypes of 60 novel thalassemia and abnormal hemoglobin (Hb) mutations discovered following the adoption of routine DNA sequencing of both α- and ß-globin genes for all UK hemoglobinopathy samples referred for molecular investigation. This screening strategy over the last 10 years has revealed a total of 11 new ß chain variants, 15 α chain variants, 19 ß-thalassemia (ß-thal) mutations and 15 α(+)-thalassemia (α(+)-thal) mutations. The large number of new thalassemia alleles confirms the wide racial heterogeneity of mutations in the UK immigrant population. Eleven of the new variants ran with Hb A on high performance liquid chromatography (HPLC), demonstrating the value of routine sequencing of both α- and ß-globin genes for all hemoglobinopathy investigations. The new ß chain variants are: Hb Bury [ß22(B4)Glu â Asp (HBB: c.69A > T)], Hb Fulwood [ß35(C1)Tyr â His (HBB: c.106T > C)], Hb Little Venice [ß42(CD1)Phe â Cys (HBB: c.128T > G)], Hb Cork [ß57(E1)Asn â Ser (HBB: c.173A > G), Hb Basingstoke [ß118(GH1)Phe â Ser (HBB: c.356T > C)], Hb Howden [ß20(B2)Val â Ala (HBB: c.62T > C)], Hb Wilton [ß41(C7)Phe â Leu (HBB: c.126C > A)], Hb Belsize Park [ß120(GH3)Lys â Asn (HBB: c.363A > T)], Hb Hampstead Heath [ß2(NA2)His â Gln;ß26(B8)Glu â Lys (HBB: c.[6C > G;79G > A])], Hb Grantham [ß85(F1)Phe â Cys (HBB: c.257T > G)] and Hb Calgary [ß64(E8)Gly â Val (HBB: c.194G > T). The new α chain variants are: Hb Edinburgh [α70(E19)Val â Gly (HBA2: c.212T > G)], Hb Walsgrave [α116(GH4)Glu â Val (HBA2: c.350A > T)], Hb Wexham [α117(GH5) and 118(H1) insertion Ser (HBA1: c.354-355insTCA)], Hb Coombe Park [α127(H10)Lys â Glu (HBA2: c.382A > G)], Hb Oxford [α17(A15)Val â Asp (HBA2: c.53T > A)], Hb Bridlington [α32(B13)Met â Thr (HBA1: c.98T > C), Hb Wolverhampton [α81(F2)Ser â Tyr (HBA2: c.9245C > A)], Hb Little Waltham [α13(A11)Ala â Asp (HBA2: c.41C > A)], Hb Derby [α61(E10)Lys â Arg (HBA1: c.185A > G)], Hb Uttoxter [α74(EF3)Tyr â Asp (HBA2: c.223G > T)], Hb Harehills [α124(H7)Ser â Cys (HBA1: c.374C > G)], Hb Hekinan II [α27(B8)Glu â Asp (HBA1: c.84G > T)], Hb Manitoba IV [α102(G9)Ser â Arg (HBA1: c.307A > C), Hb Witham [α139(HC1)Lys â Arg (HBA2: c.419A > G) and Hb Farnborough [α9(A7)Asn â Asp (HBA1: c.28A > G). In addition, 10 more paralogous α-globin chain variants have been discovered. The novel ß-thal alleles are: HBB: c.-138C > G, HBB: c.-121C > T, HBB: c.-80T > G, HBB: c.18_19delTG, HBB: c.219_220insT, HBB: c.315 + 2_315 + 13delTGAGTCTATGGG, HBB: c.316-70C > G, HBB: c.345_346insTGTGCTG, HBB: c.354delC, HBB: c.376-381delCCAGTG, HBB: c.393T > A, HBB: c.394_395insA, HBB: c.375_376insA, HBB: c.*+95_*+107delTGGATTCTinsC, HBB: c.* + 111_*+112delAA, HBB: c.*+112A > T, HBB: c.394C > T, HBB: c.271delG and HBB: c.316-3C > T. The novel α (+ )-thal alleles are: HBA1: c.95+1G > C, HBA1: c.315C > G [Hb Donnington, α104(G11)Cys â Trp], HBA1: c.327delC, HBA1: c.333_345del, HBA1: c.*+96G > A, HBA2: c.2T > G, HBA2: c.112delC, HBA2: c.143delA, HBA2: c.143_146delACCT, HBA2: c.156_157insG, HBA2: c.220_223delGTGG, HBA2: c.305T > C [Hb Bishopstown, α101(G8)Leu â His], HBA2: c.169_170delAA, HBA2: c.1A > T and HBA2: c.-3delA.
Asunto(s)
Hemoglobinopatías/genética , Mutación , Globinas alfa/genética , Globinas beta/genética , Alelos , Sustitución de Aminoácidos , Estudios de Asociación Genética , Genotipo , Hemoglobinopatías/diagnóstico , Hemoglobinopatías/epidemiología , Humanos , Fenotipo , Derivación y Consulta , Análisis de Secuencia de ADN , Reino Unido/epidemiología , Talasemia alfa/diagnóstico , Talasemia alfa/epidemiología , Talasemia alfa/genética , Talasemia beta/diagnóstico , Talasemia beta/epidemiología , Talasemia beta/genéticaRESUMEN
A molecular study of Hb Lepore heterozygotes identified by the UK population screening program has revealed four out of the five known Lepore variants. The region of homologous δ- and ß-globin gene sequence was determined in 58 unrelated Hb Lepore heterozygotes referred for confirmation of their carrier status by DNA analysis through the national thalassemia and sickle cell screening program over a period of 10 years. The most common variant found was Hb Lepore-Boston-Washington (Hb LBW, HBD: c.265 C > c.315 + 7 C) observed in 46 carriers (79.0%). Hb Lepore-Hollandia (HBD: c.69 A > c.92 + 16 A) was found in nine cases (16.0%); Hb Lepore-Baltimore (HBD: c.208 G > c.254 C) in two cases (4.0%) and Hb Lepore-ARUP (HBD: c.97 C > c.150 C) in one carrier (2.0%). Analysis of the hematological findings showed no significant differences between the four groups. The wide range of Hb Lepore variants observed in this study confirms the very diverse range of α- and ß-globin gene mutations observed in the UK population by previous studies.
Asunto(s)
Hemoglobinas Anormales/genética , Femenino , Heterocigoto , Humanos , Mutación , Reino UnidoRESUMEN
We report here the spectrum of δ-globin gene mutations found in the UK population. Nine different δ chain variants and two δ-thalassemia (δ-thal) mutations were characterized in a study of 127 alleles in patients with either a low Hb A2 value or a split Hb A2 peak on high performance liquid chromatography (HPLC). The most common δ chain variant was Hb [Formula: see text] (or Hb B2) [δ16(A13)Gly â Arg; HBD: c.49G > C] (77.0%), followed by Hb A2-Yialousa [δ27(B9)Ala â Ser; HBD: c.82G > T] (12.0%), Hb A2-Babinga [δ136(H14)Gly â Asp; HBD: c.410G > A] (3.0%), Hb A2-Troodos [δ116(G18)Arg â Cys; HBD: c.349C > T] (1.0%), Hb A2-Coburg [δ116(G18)Arg â His; HBD: c.350G > A] (2.0%) and Hb A2-Indonesia [δ69(E13)Gly â Arg; HBD: c.208G > C] (1.0%). Three novel variants were identified: Hb A2-Calderdale [codon 2 (CAT > AAT), His â Asn; HBD: c.7C > A], Hb A2-Walsgrave [codon 52 (GAT > CAT), Asp â His; HBD: c.157G > C] and Hb A2-St. George's [codon 81 (CTC > TTC), Leu â Phe; HBD: c.244C > T]. In addition, two known δ-thal mutations were observed: -68 (C > T); HBD: c.-118C > T and codon 4 (ACT > ATT); HBD: c.14C > T. Amplification refractory mutation system (ARMS) primers were developed to provide a simple molecular diagnostic test for the most common variant, Hb [Formula: see text]. Three of the variants had a characteristic HPLC retention time that can be used for a presumptive diagnosis.
Asunto(s)
Hemoglobinas Anormales/genética , Técnicas de Diagnóstico Molecular/métodos , Mutación , Globinas delta/genética , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , Reino Unido/epidemiología , Talasemia delta/diagnóstico , Talasemia delta/epidemiología , Talasemia delta/genéticaRESUMEN
We investigated whether mutations in the KLF1 gene are associated with increased Hb F levels in ethnically diverse patients referred to our laboratory for hemoglobinopathy investigation. Functionally effective KLF1 mutations were identified in 11 out of 131 adult samples with an elevated Hb F level (1.5-25.0%). Eleven different mutations were identified, 9 of which were previously unreported. KLF1 mutations were not identified in a matched cohort of 121 samples with normal Hb F levels (<1.0%). A further novel KLF1 mutation was also found in a sickle cell disease patient with a Hb F level of 20.3% who had a particularly mild phenotype. Our results indicate KLF1 mutations could make a significant contribution to Hb F variance in malarial regions where hemogobinopathies are common. All the mutations identified were heterozygous providing further in vivo evidence that a single altered KLF1 allele is sufficient to increase Hb F levels.
Asunto(s)
Hemoglobina Fetal/metabolismo , Hemoglobinopatías/genética , Hemoglobinopatías/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Mutación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/metabolismo , Niño , Preescolar , Orden Génico , Estudios de Asociación Genética , Genotipo , Humanos , Lactante , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
Prenatal diagnosis of the hemoglobinopathies by fetal DNA analysis is currently performed in most countries, either by DNA sequencing, restriction enzyme polymerase chain reaction (RE-PCR) or the amplification refractory mutation system (ARMS). These methods are time consuming and prolong the turnaround time for diagnosis. We here describe a method utilizing pyrosequencing for the prenatal diagnosis of 12 common nondeletional α- and ß-globin gene mutations in the UK population. In particular, it replaced the diagnosis of sickle cell disease by RE-PCR and for the diagnosis of ß-thalassemia (ß-thal) by Sanger DNA sequencing. We have genotyped 148 chorionic villi and 29 uncultured amniotic fluid DNA samples by pyrosequencing and found 100% concordance with the fetal diagnosis result obtained by ARMS-PCR or DNA sequencing. Pyrosequencing was more robust, revealing an 83% decrease in diagnostic failures using uncultured amniocyte DNA samples, and also quantitative, revealing one case of allelic imbalance due to maternal DNA contamination. Overall, we found pyrosequencing to be simpler, more robust, quicker, and less expensive than conventional sequencing and RE-PCR, making it a good choice for rapid and cost-effective prenatal diagnosis of thalassemia and sickle cell disease.
Asunto(s)
Hemoglobinopatías/diagnóstico , Diagnóstico Prenatal , Análisis de Secuencia de ADN/métodos , Globinas alfa/genética , Globinas beta/genética , Líquido Amniótico/química , Secuencia de Bases , Muestra de la Vellosidad Coriónica , Femenino , Genotipo , Técnicas de Genotipaje , Hemoglobinopatías/epidemiología , Hemoglobinopatías/genética , Humanos , Datos de Secuencia Molecular , Embarazo , Reino Unido/epidemiologíaRESUMEN
We have characterized a newly identified 16.6 kb deletion which removes a significant proportion of the human alpha-globin cluster including the psizeta1, alpha(D), psialpha1 and alpha2-globin genes but leaves the duplicated alpha1 gene intact. This complicated rearrangement results from a combination of slippage and strand switching at sites of microhomology during replication. Functional analysis shows that expression of the remaining alpha1 gene is increased, rather than down-regulated by this deletion. This could be related to its proximity to the remote upstream alpha-globin regulatory elements or reduced competition for these elements in the absence of the dominant alpha2-globin gene. The finding of a very mild phenotype associated with such an extensive deletion in the alpha-globin cluster implies that much of the DNA removed by the deletion is likely to be functionally unimportant. These findings suggest that other than the upstream regulatory elements and promoter proximal elements there are unlikely to be additional positive cis-acting sequences in the alpha-globin cluster.
Asunto(s)
Replicación del ADN , Eliminación de Gen , Globinas/genética , Familia de Multigenes , Adulto , Células Cultivadas , Niño , Cromatina/genética , Cromatina/metabolismo , Cromosomas Humanos Par 16/genética , Femenino , Expresión Génica , Globinas/metabolismo , Humanos , Masculino , Fenotipo , ARN Polimerasa II/metabolismoRESUMEN
Beta-thalassemia (beta-thal) is one of the most common autosomal recessive disorders in Iran, with more than 15,000 registered cases of thalassemia major in the country. Iran has a multiethnic society and knowledge of the mutation spectrum and regional distribution is an essential requirement for health planning and a prenatal diagnosis program. We have determined the spectrum of mutations in patients from the Isfahan region of Iran. A study of 190 chromosomes revealed 24 different mutations, including three novel ones: -41 (A>C), IVS-I-109 (-T) and codon 24 (-G). The most common mutation was IVS-II-1 (G>A) (20.5%), followed by IVS-I-5 (G>C) (11%). The findings for the Isfahan region confirm the extremely heterogeneous nature of the molecular basis of beta-thal in Iran. The results show that a strategy of using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) for 14 of the most common mutations and DNA sequencing for the rare mutations can be used for prenatal diagnosis of beta-thal in this region.
Asunto(s)
Alelos , Codón/genética , Mutación Puntual , Globinas beta/genética , Talasemia beta/genética , Análisis Mutacional de ADN , Humanos , Irán , Reacción en Cadena de la Polimerasa , Talasemia beta/diagnósticoRESUMEN
We have identified and characterized a novel beta-globin gene deletion mutation in a family of Afghan ancestry. The proband was a 10-year-old transfusion-dependent female with the phenotype of beta-thalassemia major (beta-TM). DNA sequencing of the beta-globin gene showed no abnormalities. Multiplex ligation-dependent probe amplification (MLPA) showed reduced/absent probe height of the probe covering the 5' end of the beta-globin gene indicating a possible deletion. Gap-polymerase chain reaction (gap-PCR) produced junctional fragments and direct sequencing of the product revealed that the 5' breakpoint was 478 nucleotides upstream of the Cap site and the 3' breakpoint was in the second exon of the beta-globin gene, giving a deletion size of 909 bp. The proband was homozygous and the parents were heterozygous for the deletion. This is the first report of a large beta-thalassemia (beta-thal) deletion mutation in this ethnic group.
Asunto(s)
Eliminación de Gen , Globinas beta/genética , Talasemia beta/genética , Adulto , Afganistán , Niño , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , MasculinoRESUMEN
Large deletions of the beta-globin gene cluster are problematic to diagnose, and consequently the frequency and range of these mutations in the UK is unknown. Here we present a study evaluating the efficacy of the recently available technique of multiplex ligation-dependent prob amplification (MLPA) to determine the range and frequency of these deletions in the UK population. The results revealed a large deletion mutation in 75 of 316 patient samples collected over a 3-year period. Of these, 52 had a common (deltabeta)(0)-thalassemia [(deltabeta)(0)-thal] or hereditary persistence of fetal hemoglobin (HPFH) allele and 23 had rare or novel deletions resulting in (epsilon(G)gamma(A)gammadeltabeta)(0)-thal, (G)gamma(A)gamma(deltabeta)(0)-thal and beta(0)-thal. A total of 17 different deletions were found, 10 of which were rare and four were most likely novel [Asian Indian (epsilon(G)gamma(A)gammadeltabeta)(0)-thal, African (deltabeta)(0)-thal, African beta(0)-thal and Afghanistani beta(0)-thal]. The MLPA technique detected examples from all four categories of beta-globin gene deletions and demonstrated the wide molecular basis of deletional beta-thal/HPFH in UK patients.
Asunto(s)
Eliminación de Gen , Hemoglobinas Anormales/genética , Mutación , Técnicas de Amplificación de Ácido Nucleico/métodos , Globinas beta/genética , Hemoglobina Fetal/genética , Frecuencia de los Genes , Hemoglobinopatías/epidemiología , Hemoglobinopatías/etnología , Hemoglobinopatías/genética , Humanos , Talasemia/genética , Reino Unido/epidemiología , Reino Unido/etnologíaRESUMEN
Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. Carrier identification and prenatal diagnosis represent valuable procedures that identify couples at risk for having affected children, so that they can be offered options to have healthy offspring. Molecular diagnosis facilitates prenatal diagnosis and definitive diagnosis of carriers and patients (especially 'atypical' cases who often have complex genotype interactions). However, the haemoglobin disorders are unique among all genetic diseases in that identification of carriers is preferable by haematological (biochemical) tests rather than DNA analysis. These Best Practice guidelines offer an overview of recommended strategies and methods for carrier identification and prenatal diagnosis of haemoglobinopathies, and emphasize the importance of appropriately applying and interpreting haematological tests in supporting the optimum application and evaluation of globin gene DNA analysis.