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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a sensitive, reliable and reproducible method, based on three multiplex PCR assays, for the rapid detection of seven common alpha-thalassaemia deletions and one alpha-globin gene triplication. The new assay detects the alpha0 deletions - -SEA, - (alpha)20.5, - -MED, - -FIL and - -THAI in the first multiplex PCR, the second multiplex detects the -alpha3.7 deletion and alphaalphaalphaanti3.7 variant, the third multiplex detects the -alpha4.2 deletion. This simple multiplex method should greatly facilitate the genetic screening and molecular diagnosis of these determinants in populations where alpha-thalassaemias are prevalent.
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PMID:Rapid detection of alpha-thalassaemia deletions and alpha-globin gene triplication by multiplex polymerase chain reactions. 1069 58

Seven unrelated patients with hemoglobin (Hb) H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha)20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, alphaalphaNcoI, alphaIcalpha and alphaTSaudialpha) was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha)20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(alphaalpha)T]. Among the 27 patients with structural alterations, 15 (of Italian descent) had Hb Hasharon (alpha47Asp-->His) associated with the -alpha3.7 deletion, 4 (of Italian descent) were heterozygous for Hb J-Rovigo (alpha53Ala-->Asp), 4 (3 Blacks and 1 Caucasian) were heterozygous for Hb Stanleyville-II (alpha78Asn-->Lys) associated with the alpha+-thalassemia, 1 (Black) was heterozygous for Hb G-Pest (alpha74Asp-->Asn), 1 (Caucasian) was heterozygous for Hb Kurosaki (alpha7Lys-->Glu), 1 (Caucasian) was heterozygous for Hb Westmead (alpha122His-->Gln), and 1 (Caucasian) was the carrier of a novel silent variant (Hb Campinas, alpha26Ala-->Val). Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.
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PMID:alpha-globin genes: thalassemic and structural alterations in a Brazilian population. 1097 35

The purpose of this study was to examine the frequency of alpha-thalassemia in the population of Cyprus using cord blood samples. The levels of Hb Bart's were compared with the hematological indices and the results correlated with the presence of alpha-thalassemia mutations. The protocols for the polymerase chain reaction detection of the six most common alpha-globin mutations encountered in Cyprus were optimized, and the frequency of each mutation was determined through the screening of 495 random cord blood samples. The total allele frequency for the mutations examined was 10.6%, of which 1% is due to the triplication of the alpha-globin genes. The -alpha(3.7 kb) deletion accounts for 72.8% of all detectable mutations, while the--MED-I and -(alpha)-20.5 kb mutations account for 7.8%. The level of Hb Bart's and the MCV and MCH values in cord blood samples were found to correlate closely with the severity of alpha-thalassemia, although the -alpha(3.7 kb) deletion and perhaps other mild alpha-thalassemia mutations may not give detectable Hb Bart's levels. A reasonably accurate estimate of the alpha-thalassemia carrier frequency may be obtained from cord blood studies if Hb Bart's estimates are combined with hematological indices. When molecular methods are added, these give the best way to use cord bloods to survey populations for alpha-thalassemia.
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PMID:Hb Bart's levels in cord blood and alpha-thalassemia mutations in Cyprus. 1097 37

We studied 15 Sicilian subjects with Hb H disease correlating clinical examinations with hematological and molecular data. Seven different alpha-tha1 mutations were identified: four deletion types (--MED --CAL, -alpha3.7, -alpha4.2) and three nondeletion types (alpha(Ncol)alpha, alpha(Hph)alpha, alphaCSalpha). All the patients had a zero-gene chromosome (--MED or --CAL), while the third alpha gene was deleted (-alpha3.7, -alpha4.2) or inactive (alpha(Ncol)alpha, alpha(Hph)alpha, alphaCSalpha). In patients with the nondeletion genotype the analysis of hematological values revealed lower levels of RBC and Hb A2 and significantly higher levels of Hb H. The clinical variability was remarkable, ranging from totally asymptomatic conditions, casually diagnosed, to severe thalassemia intermedia with marked hemolytic crises, liver and spleen enlargement and the necessity for frequent transfusions. The genotype did not justify the gravity of the phenotype in every case, and the differences in clinical manifestations, also notable, are not easily explainable in subjects who apparently have the same genotype.
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PMID:Phenotype-genotype correlation in Sicilian patients with Hb H. 1109 60

In order to determine the contribution of alpha-thalassemia to microcytosis and hypochromia, 339 adult outpatients seen at Unicamp University Hospital (with the exception of the Clinical Hematology outpatient clinics), who showed normal hemoglobin (Hb) levels and reduced mean corpuscular volume and mean corpuscular hemoglobin, were analyzed. Ninety-eight were Blacks (28.9%) and 241 were Caucasians (71.1%). In all cases, Hb A2 and F levels were either normal or low. The most common deletional and nondeletional forms of alpha-thalassemia [-alpha3.7, -alpha4.2, --MED, -(alpha)20.5, alphaHphIalpha, alphaNcoIalpha, alphaalphaNcoI and alphaTSAUDI] were investigated by PCR and restriction enzyme analyses. A total of 169 individuals (49.9%) presented alpha-thalassemia: 145 (42.8%) were heterozygous for the -alpha3.7 deletion (-alpha3.7/alphaalpha) and 18 (5.3%) homozygous (-alpha3.7/-alpha3.7), 5 (1.5%) were heterozygous for the nondeletional form alphaHphIalpha (alphaHphIalpha/alphaalpha), and 1 (0.3%) was a --MED carrier (--MED/alphaalpha). Among the Blacks, 56 (57.1%) showed the -alpha3.7/alphaalpha genotype, whereas 12 (12.2%) were -alpha3.7/-alpha3.7 and 1 (1.0%) was an alphaHphIalpha carrier; among the Caucasians, 89 (36.9%) were -alpha3.7/alphaalpha, 6 (2.5%) had the -alpha3.7/-alpha3.7 genotype, 4 (1.7%) presented the nondeletional form (alphaHphIalpha/alphaalpha), and 1 (0.4%) was a --MED carrier. These results demonstrate that alpha-thalassemia, mainly through the -alpha3.7 deletion, is an important cause of microcytosis and hypochromia in individuals without anemia. These data are of clinical relevance since these hematological alterations are often interpreted as indicators of iron deficiency.
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PMID:High prevalence of alpha-thalassemia among individuals with microcytosis and hypochromia without anemia. 1137 64

This work compiles the results of our research on alpha- and beta-thalassemias, and includes a literature review of the molecular genetics of alpha- and beta-thalassemias in Spain. We studied 1,564 subjects with thalassemia (294 with beta-thalassemia and 1,264 with alpha-thalassemia) by molecular biology techniques. In relation to beta-thalassemia, a total of 15 different mutations were characterized in a study of 308 chromosomes belonging to 294 unrelated subjects. Eleven were homozygotes (22 alleles), three compound heterozygotes (6 alleles), and the remaining 280 were heterozygotes (280 alleles). A total of 86.6% of the alleles identified can be grouped into five different mutations [IVS-I-1 (G-->A), IVS-I-6 (T-->C), IVS-I-110 (G-->A), codon 39 (C-->T), codons 8/9 (+G)]. In 14 subjects (4.5%), all heterozygotes, it was not possible to identify the alteration responsible for the beta-thalassemia. For alpha-thalassemia, 911 subjects showed heterozygous alpha(+)-thalassemia (872 with -3.7 kb; 14 with -4.2 kb; two with the deletion of 3.5 kb of DNA, and 23 with nondeletional alpha-thalassemia). Two hundred and thirty-three subjects had homozygous alpha(+)-thalassemia (223 for -alpha(-3.7)/-alpha(-3.7)); one for -alpha(-4.2)/-alpha(-4.2); six for -alpha(-3.7)/-alpha(-4.2); one for -alpha(-3.5)/-alpha(-3.7); one for alphaalpha(Nco)/alphaalpha(Nco); one for alpha(HPh)/alpha(Hph)). One hundred patients presented with heterozygous alpha(0)-thalassemia (18 of whom were progenitors of patients with Hb H disease). The alpha(0) determinant was found in 20 patients with Hb H disease associated with -alpha(-3.7). From the DNA analysis were identified the - -(MED), - -(SEA), - -(SPAN) deletions and the - -(MA) mutations; in three cases, a break that affects the distal portion of the short arm of chromosome 16; one of these was associated with the ATR-16 (alpha-thal with mental retardation) syndrome. Triplication of the alpha genes (alphaalphaalpha(-3.7)/alphaalpha) was found in 25 subjects, 16 of whom were associated with a heterozygous beta-thalassemia. Only one patient was homozygous for the triplication of alpha genes (alphaalphaalpha(-3.7)/alphaalphaalpha(-3.7)) that was associated with a heterozygous beta-thalassemia. In the Mediterranean region preventive programs for thalassemia, based on the detection of heterozygote carriers and genetic advice, are not sufficient to reduce the incidence of newborns with major thalassemia. Prenatal diagnosis of thalassemias has given a new dimension to the prevention of these, but in order to implement this, a knowledge of the mutations and the incidence of these, is essential. This study, therefore, aims to give a general picture of the molecular genetics of thalassemia and its geographical distribution in our area.
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PMID:The thalassemia syndromes: molecular characterization in the Spanish population. 1157 Jul 20

To date, more than 35 single or oligonucleotide mutations of the alpha genes that cause alpha thalassaemia have been described. Their interactions give rise to widely variable clinical manifestations, from a mild hypochromic, microcytic anaemia to a lethal intrauterine anaemia associated with hydrops fetalis. Understanding the molecular genetics enables accurate genotyping, genetic counselling and prenatal testing for the most severe forms of alpha thalassaemia. Here we show for the first time that the interaction between two relatively common forms of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)) may be associated with a clinically severe form of alpha thalassaemia, Hb H hydrops fetalis.
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PMID:Hb H hydrops fetalis syndrome associated with the interaction of two common determinants of alpha thalassaemia (--MED/(alpha)TSaudi(alpha)). 1202 55

We tested 67 Iranian individuals, presenting with low mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels, normal hemoglobin electrophoresis and iron status, for the presence of twelve common alpha-thalassemia gene deletions and point mutations. Five different mutations (-alpha(3.7), -alpha(4.2), --MED, -(alpha)20.5, Hb Constant Spring) were identified in a total of 43 cases
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PMID:alpha-globin gene deletion and point mutation analysis among in Iranian patients with microcytic hypochromic anemia. 1455 21

Although alpha0-thalassemia (thal) defects are not very frequent in the Iranian population, Hb H disease does occur in the country. We have analyzed the alpha gene cluster of 13 patients showing the presence of Hb H to establish the molecular background of this disease in southwest Iran (Shiraz and Hormozgan provinces). Using gap-polymerase chain reaction (gap-PCR) and direct DNA sequencing we have found the --MED-I deletion, the polyadenylation signal (poly A) mutations alphaT-Saudi alpha and alphaT-Turkish alpha and Hb Constant Spring (Hb CS) in association with the common -alpha3.7 deletion. This study has revealed that: 1) at least six genotypes are responsible for Hb H disease in the area: .-alpha3.7/ --MED-I; -alpha3.7/alphaT-Saudi alpha; alphaT-Saudi alpha/alphaT-Saudi alpha; alphaCSalpha/--MED-I; --MED-I/alphaT-Turkish alpha; and the atypical forms of Hb H disease -alpha3.7/alphaCSalpha. 2) The molecular background of Hb H disease in the southwest area of Iran is more similar to the Mediterranean type than to the Southeast Asian. 3) Hb Bart's hydrops fetalis syndrome and mild, intermediate or severe postnatal Hb H disease conditions can be expected, but at a relatively low incidence. 4) The diagnostic flowchart for patients with microcytic hypochromic anemia should include iron deficiency, beta-thal, alpha+- and alpha0-thal analyses.
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PMID:Molecular basis of Hb H disease in southwest Iran. 1576 54

We analyzed the prevalence of alpha-thalassemia mutations in 298 subjects from Eastern Sicily (Italy) with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), normal HbA2 and HbF, and normal serum iron. In 131 subjects (43.9%) we found six different genotypes of alpha-thalassemia: -alpha3.7/alphaalpha (36.6%), -alpha3.7/-alpha3.7 (27.5%), -(MED)/alphaalpha (10.0%), -alpha20.5/alphaalpha (9.1%), alphaHphIalpha/alphaalpha (8.4%), alphaHphIalpha/alphaHphIalpha (6.1%), and -alpha3.7/alphaHphIalpha (2.3%). Our data underline that in Eastern Sicily populations, the molecular screening of alpha-thalassemia mutations and/or deletions may be useful to better characterize the clinically asymptomatic subjects with a slightly reduced MCV and MCH and normal iron status.
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PMID:Identification of alpha-thalassemia mutations in subjects from Eastern Sicily (Italy) with abnormal hematological indices and normal Hb A2. 1695 27


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