Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemoglobinopathies are the most commonly inherited genetic disorders in India. Population screening has identified certain communities in India with high risk of beta-thalassemia, the prevalence of carrier status in some being as high as 17%. Over a period of 6 years we have conducted DNA analysis on 1,233 carriers of 23 beta-thalassemia mutations and Hb E, using the amplification refractory mutation system. The studies included analyses of five common mutations for Asian Indians, namely IVS-I-5 (G-->C), 619 bp deletion, IVS-I-1 (G-->T), and the frameshifts at codons 8/9 (+G) and 41/42 (-TTCT). The occurrence of these was seen in 1,066 (86.45%) of the carriers referred to us, the percentage of mutations varying between 5.03-42.58%. We found codon 15 (TGG-->TAG) in 47 (3.81%) samples which was also considered a common mutation in the Indian population. Rare beta-thalassemia mutations were found in 87 (7.06%) individuals. We have designed five new primers and modified four primers for nine rare mutations. These were seen in nine (0.73%) samples. The beta-thalassemia anomaly in 33 (2.68%) carriers remained uncharacterized. State-wide and community-wide distribution patterns of mutations indicated that IVS-I-5 (G-->C) is the most common beta-thalassemia allele in the Indian population. Sindhis settled in Gujrat, and Maharashtra and Lohanas from Gujrat showed a prevalence of the 619 bp deletion mutation in 49.2 and 45.5% carriers, respectively. High frequency of the IVS-I-1 (G-->T) mutation was also found in Sindhis (25.5%), Punjabi Hindus (34.7%), and Lohanas (31.2%). These studies of mutation patterns in different communities have helped us in the quick identification of beta-thalassemia mutations for prenatal diagnosis.
 ...
PMID:Distribution of beta-thalassemia mutations in the Indian population referred to a diagnostic center. 1097 38

We describe the characterization of an alpha+-thalassaemia determinant as a result of a transition of G-->A of the donor splice consensus site sequence of the first intron of the alpha1-globin gene (alpha1IVS I-1). The mutation was found in combination with the South-East Asian alpha0-thalassaemia deletion in an haemoglobin (Hb)H patient and her sister, both of Thai origin. Sequencing of the abnormally spliced mRNA product revealed the presence of a cryptic splice site in exon 1 of the alpha1-globin gene. No normally spliced alpha1mRNA was detected. The abnormally spliced mRNA product from the alpha1-gene carrying the mutation does not lead to functional protein and causes a mild HbH-disease phenotype when in combination with the deletion type alpha0-thalassaemia.
 ...
PMID:alpha-thalassaemia as a result of a novel splice donor site mutation of the alpha1-globin gene. 1099 82

The aim of the present study was to evaluate the point mutations of beta-thalassemia patients from the Aegean region of Turkey by using an allele-specific oligonucleotide hybridization technique. DNA isolated from peripheral blood samples of 75 children with beta-thalassemia major or intermedia was analyzed using a Bio-Rad mD(x)(TM)-Be Tha Gene 1 kit. We determined mutations in 56 (74.6%) patients. The allelic frequency of mutations in 150 chromosomes was as follows: IVS-I-110 (G-A) 44.1%, IVS-I-1 (G-A) 28.2%, IVS-I-6 (T-C) 13.3%, IVS-II-745 (C-G) 9.3%, IVS-II-1 (G-A) 2.7%, Cd 39 (C-T) 2.4%, -87 (C-G) 0% and Cd 6 (-A) 0%. The distribution of the mutation types was consistent with the findings of other research groups.
 ...
PMID:Mutational analysis of beta-thalassemia cases from the Aegean region of Turkey using an allele-specific oligonucleotide hybridization technique. 1127 8

In Thailand and adjacent countries, most of the beta-thalassemia genes are beta(0)-thalassemia mutations that prevent the production of Hb A. We propose the quantitation of the Hb A fraction in fetal blood in the mid-trimester of pregnancy by automated high performance liquid chromatography as a reasonable prenatal diagnostic method to be applied in areas with limited laboratory facilities. Forty pregnant women at risk of delivering a child with beta-thalassemia major were identified using an erythrocyte osmotic fragility test and quantitation of Hb A2. Cordocentesis was performed at the gestational age of 18-22 weeks and fetal blood was analyzed for hemoglobin fractions by automated high performance liquid chromatography. The beta-globin gene mutations were characterized by beta-globin gene sequencing. The 4 bp deletion at codons 41/42 (-TTCT) was the most frequent of the 40 beta-thalassemia mutations observed (20/40 = 50%), followed by the splice site mutation IVS-I-1 (G-->T) (7/40 = 17.5%), the nonsense mutation at codon 17 (A-->T) (7/40 = 17.5%), the nonsense mutation at codon 35 (C-->A) (3/40 = 7.5%), and the beta(+)-thalassemia promoter mutation at -28 (A-->G) (3/40 = 7.5%). High performance liquid chromatography revealed nine fetuses which had only Hb F and no Hb A. All were homozygotes or compound heterozygotes for beta(0)-thalassemia mutations. In the remaining 31 fetuses, a Hb A peak was present in the chromatograms. One fetus with 0.5% Hb A was a compound heterozygote for the -28 (A-->G) and codons 41/42 (-TTCT) mutations. In the remaining 30 fetuses, the Hb A values ranged between 0.8 and 7.4%. Twenty of these, with a Hb A concentration of 1.82 +/- 0.49% (range 0.8-2.8%), were beta-thalassemia heterozygotes. The remaining 10 fetuses had Hb A values of 4.89 +/- 1.47% (range 2.9-7.4%) and normal beta-globin genes. The absence of Hb A in homozygotes or compound heterozygotes for beta(0)-thalassemia mutations and the presence of measurable amounts of Hb A in heterozygotes and normal homozygotes, permits the diagnosis of fetuses expected to develop postnatal beta-thalassemia major.
 ...
PMID:Prenatal diagnosis of beta-thalassemia major by high-performance liquid chromatography analysis of hemoglobins in fetal blood samples. 1130 Mar 46

Prevention of beta-thalassemia implies knowledge of the molecular spectrum occurring in the population at risk. This knowledge is necessary, especially when a prevention protocol is applied to a multiethnic population. For this purpose, we have recently analyzed a large population of Iranian patients living in the Province of Hormozgan in Iran, and a small group of Iranian patients living in The Netherlands. We have found a different mutation spectrum in both populations as compared to the data obtained by other authors for the Iranian regions of Tehran, Fars, Sistan Balouchestan, Bushehr, and Khouzestan. The IVS-I-5 (G-->C) is the most frequent mutant in the province of Hormozgan (69%), followed by the IVS-II-1 (G-->A) (9.6%), while the IVS-I-1 (G-->A) was the most frequent defect found in the Iranian population sample in The Netherlands. The IVS-II-745 (C-->G) mutation in cis with the 5'UTR (untranslated region) +20 (C-->T) transition was observed in two unrelated, transfusion-dependent homozygotes, living in the Hormozgan Province where, in contrast with populations living in other provinces of Iran, no IVS-I-110 (G-->A) or IVS-I-1 (G-->A) mutations were found. We report the molecular spectra of our population samples and compare them with the mutation spectra observed in the Iranian populations by other authors. We discuss the severe phenotype of the patients homozygous for the IVS-II-745 (C-->G) mutation, linked in cis to the 5'UTR +20 (C-->T) transition. Molecular analysis using commercial kits is briefly compared with denaturing gradient gel electrophoresis, emphasizing the value of a rapid method of detection for molecular defects in areas where many mutations occur.
 ...
PMID:Molecular spectrum of beta-thalassemia in the Iranian Province of Hormozgan. 1130 Mar 48

Beta-thalassemia is the most common genetic abnormality causing health problems worldwide. Cukurova, in the southern part of Turkey, being on the Mediterranean, is in the thalassemic belt. Since there is no cure for the disease at present, the frequency of the mutation types of beta-thalassemia must first be identified to aid in clinical follow-up and prenatal diagnosis. Carriers identified during a screening survey and patients referred to our laboratory were studied for this purpose. After routine hematological analysis molecular screening was performed by the amplification refractory mutation system and DNA sequencing. The frequency of the common mutations were: IVS-I-110 (G-->A) 57.3%, IVS-I-1 (G-->A) 8.3%, codon 39 (C-->T) 6.4%, IVS-I-6 (T-->C) 5.7%, frameshift codon 8 (-AA) 5.7%, -30 (T-->A) 4.7%, IVS-II-1 (G-->A) 3.4%, IVS-II-745 (G-->C) 2.8%, and frameshift codon 5 (-CT) 1.1%. Some rare mutations (1%) such as frameshift codon 44 (-C) 0.7%, frameshift codons 74/75 (-C) 0.7%, IVS-1-5 (G-->C) 0.7%, frameshift codons 8/9 (+G) 0.4%, frameshift codons 36/37 (-T) 0.4%, frameshift codons 22/23/24 (-AAGTTGG) 0.4%, IVS-1-130 (G-->C) 0.4%, IVS-1-5 (G-->T) 0.2%, -28 (A-->C) 0.2%, codon 15 (TGG-->TGA) 0.2%, and frameshift codons 82/83 (-G) 0.2%, were detected by sequence analysis. The codon 15 (TGG-->TGA) and frameshift codons 82/83 (-G) mutations were seen in Turkey for the first time.
 ...
PMID:Genetic heterogeneity of beta-thalassemia at Cukurova in southern Turkey. 1148 Jul 85

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.
 ...
PMID:The thalassemia syndromes: molecular characterization in the Spanish population. 1157 Jul 20

A study of the spectrum of beta-thalassemia mutations in the southern part of the West Bank of the Palestinian Authority revealed the presence of 10 different beta-globin mutations. The study included 41 patients and 54 carriers of beta-thalassemia and sickle cell anemia. The spectrum of mutations observed was typically Mediterranean. However, their relative frequencies was unique. The predominant allele was IVS-I-6 (T-->C), with an exceptionally high frequency of 48.5% for this mutation. The homozygous IVS-I-6 patients had widely variable clinical presentations, from typical transfusion-dependent thalassemia major to non-transfusion-dependent thalassemia intermedia phenotype. Since it is so widespread in these West Bank populations, the IVS-I-6 mutation may date back to ancient times. The nonsense mutation at codon 37 (G-->A) was found at a relatively high frequency of 11.3%, supporting the hypothesis that it originated in this region. The other mutations, at decreasing frequencies ranging from 9.5-1.5%, were: IVS-I-110 (G-->A), frameshift codon 5 (- CT), IVS-I-1 (G-->A), IVS-II-1 (G-->A), Hb S [beta6(A3)Glu-->Val], frameshift codons 8/9 (+G), codon 39 (C-->T), and -30 (T-->A). Our findings will improve health care for the Palestinian population, and also has implications for the study of the origin and spread of thalassemia in the Middle East.
 ...
PMID:The beta+-IVS-I-6 (T-->C) mutation accounts for half of the thalassemia chromosomes in the Palestinian populations of the mountain regions. 1193 10

The coexistence of beta- and gamma-globin gene mutations in the compound heterozygous state presents a rare in vivo model that provides important data on gene regulation of clinical interest. In this unique comparative study we present the hematological, biosynthetic, and molecular data from six adult compound heterozygotes for the Greek nondeletional hereditary persistence of fetal hemoglobin (nd-HPFH, Agamma-117 G-->A) and four frequent beta-thalassemia mutations (IVS I-110 G-->A, Cd 39 C-->T, IVS I-1 G-->A, and IVS I-6 T-->C) found in the Hellenic population. Fetal hemoglobin (HbF) levels were found to be considerably higher (25-50%) than in 19 Greek nd-HPFH heterozygotes (HbF=9.7+/-1.7%) and, interestingly, to depend on the type of the respective beta-thalassemia mutation, in trans to the nd-HPFH allele. All cases presented a typical beta-thalassemia heterozygote's phenotype despite the increased HbF and the normal HbA2 levels, as indicated by both the hematological indices and the biosynthetic ratios. These data were compared with those from two unique cases of Greek origin: a homozygous case of the Greek nd-HPFH and a compound heterozygote with HbS. Our data suggest that in these compound heterozygous cases the beta-thalassemic chromosome indirectly determines the final outcome of the gamma- and of the in cis beta-globin gene expression, most likely at the post-transcriptional level.
 ...
PMID:A comparative study of Greek nondeletional hereditary persistence of fetal hemoglobin and beta-thalassemia compound heterozygotes. 1197 33

The preliminary results of a pilot study are reported, intended as an initiation of a research plan, focused on the prevention of beta-thalassemia in Iran. The aims of this study are: (i) to improve the knowledge of the molecular background of beta-thalassemia intermedia in Southern Iran; (ii) to verify the role of the -158 (G)gamma (C-->T) (Xmn I) polymorphism as a modulating factor in thalassemia intermedia; (iii) to test the validity of the multiplex and single mutation specific amplification refractory mutation system in analyzing the molecular defects causing beta-thalassemia in multiethnic populations; and (iv) to develop suitable strategies for the application of prevention protocols in Iran. To accomplish the task we have selected 87 beta-thalassemia intermedia patients and adapted the DNA methodology to detect the following 11 frequent mutations in Iran: codon 5 (-CT); frameshift codons (FSC) 8/9 (+G); codon 30 (G-->C); IVS-I-1 (G-->A); IVS-I-5 (G-->C); IVS-I-6 (T-->C); IVS-I-110 (G-->A); codons 36/37 (-T); codon 44 (-C); IVS-II-1 (G-->A); IVS-II-745 (C-->G). Because of the multiethnicity of the population we have also included the Indian IVS-I (25 bp deletion) and the Mediterranean IVS-I-130 (G-->C) and codon 39 (C-->T) mutations. Forty-eight patients were randomly studied for the Xmn I polymorphism together with 50 healthy volunteers as a control group. The molecular analysis conducted in Iran, identified only 31% of the alleles that were presumed to be thalassemic, revealing either a strategic or a technical insufficiency of the chosen method. However, the mutations with the highest prevalence in the country (IVS-II-1, IVS-I-110, IVS-I-1 and FSC 8/9) were found. As expected the IVS-II-1 defect, being the most frequent in south Iran, was present at the highest rate (24%). The Xmn I polymorphism was found in association with this prevalent mutation and was detected in the homozygous state in 87.5% of the patients homozygous for the IVS-II-1 (G-->A) mutation. The overall positivity for Xmn I was found in 40.6% of the thalassemic alleles vs. 14% in the non-thalassemic, confirming the hypothesis of an older event, antecedent to the IVS-II-1 mutation. In trying to assess a more suitable molecular detection method we intend to continue this study in collaboration with the European centers involved, applying more effective technologies and better defining the molecular spectrum of beta-thalassemia in the sub-populations. We also intend to verify the effect of alpha-thalassemia in the genotype/phenotype correlation of beta-thalassemia intermedia.
 ...
PMID:Beta-thalassemia intermedia from southern Iran: IVS-II-1 (G-->A) is the prevalent thalassemia intermedia allele. 1214 57


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>