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)

Hemoglobin (Hb) gene disorders are one of the most common inherited diseases in Taiwan, which include alpha-thalassemia, beta-thalassemia, and Hb variants. In this study, we collected and analyzed mutations found in 930 patients with Hb gene disorders except Hb Bart's Hydrops and beta-thalassemia major. The patients included 650 cases of alpha-thalassemia, 225 cases of beta-thalassemia, 9 cases of alpha-thalassemia combined with beta-thalassemia, and 46 cases of Hb variants or Hb variants combined with alpha-thalassemia or beta-thalassemia. The most common type of alpha0-thalassemia and alpha++-thalassemia mutations in our study were the SEA type deletion and the alpha3.7 deletion, respectively; the most common beta-thalassemia mutation was the IVS-2 nt 654 C-->T mutation; and the most common Hb variant was the HbE. We compared the relationships between genotype and hematological phenotypes of various Hb gene disorders and found that different genotypes of alpha0-thalassemia have similar hematological features. In conclusion, the results of our study provide data of the complex interaction of thalassemias and Hb variants which might be useful for other researchers in this field.
 ...
PMID:Hematological features and molecular lesions of hemoglobin gene disorders in Taiwanese patients. 1871 Apr 11

The objective of this study was to compare red blood cell indices among normal, alpha-thalassemia-1 trait, and hemoglobin (Hb) Bart's fetuses at mid-pregnancy. A total of 87 pregnancies (88 fetuses) at risk of homozygous alpha-thalassemia-1, who underwent cordocentesis including the measurement of Hb level and red blood cell indices of fetuses at 18-22 weeks of gestation at Maharaj Nakorn Chiang Mai Hospital, were recruited into this study. The final outcome was based on the fetal DNA analysis using PCR technique for SEA type alpha-thalassemia-1. Fetuses were divided into three groups: normal, alpha-thalassemia-1 trait, and homozygous alpha-thalassemia-1 (Hb Bart's disease). The mean gestational age of the 87 pregnant women recruited into the study was 18.7 +/- 0.8 weeks. According to the DNA analysis, the incidence of Hb Bart's disease, alpha-thalassemia-1 trait, and normal fetuses were 29.5%, 45.5%, and 25%, respectively. The mean Hb level, mean corpuscular volume, mean corpuscular Hb, and mean cell Hb concentration were significantly different in all three groups of fetuses. Moreover, these differences were also found among fetuses with the alpha-thalassemia-1 trait and those that were normal. Ninety-two percent of fetuses with Hb Bart's disease had some degree of anemia at mid-pregnancy. However, two Hb Bart's fetuses did not have anemia. Furthermore, two fetuses in the alpha-thalassemia-1 trait group were mildly anemic, but most (95%) were not. There is a highly significant difference in red blood cell indices among normal, alpha-thalassemia-1 trait, and Hb Bart's fetuses, and most fetuses with Hb Bart's disease have some degree of anemia from mid-pregnancy.
 ...
PMID:Comparison of red blood cell hematology among normal, alpha-thalassemia-1 trait, and hemoglobin Bart's fetuses at mid-pregnancy. 1893 92

Molecular analysis of two fetuses at high risk of alpha-thalassemia (alpha-thal), and their family members, was performed using real-time polymerase chain reaction (PCR) with SYBR Green 1 (SYBR-PCR) dye combined with dissociation curve analysis and multiplex PCR (m-PCR) and DNA sequencing techniques. The genotype of the fetus from one family was --SEA/--SEA (Southeast Asian deletion), which produces hydrops fetalis syndrome. The genotype of the parents was --SEA/alphaalpha. A boy with Hb H disease and his sibling fetus from the other family had the genotype --SEA/alphaCSalpha [the Hb Constant Spring (CS) mutation: alpha142, Term-->Gln (TAA>CAA in alpha2)] and alphaalpha/alphaalpha (normal), respectively. The diagnosis, based on SYBR-PCR combined with dissociation curve analysis, was in agreement with the results from the m-PCR method. This indicates that these are alternative and reliable assays for the molecular diagnosis of deletional alpha-thal.
 ...
PMID:Molecular prenatal diagnosis of alpha-thalassemia using real-time and multiplex polymerase chain reaction methods. 1906 33

The multiplex ligation-dependent probe amplification (MLPA) method was used to analyze 118 DNA samples from 90 alpha-thalassemia (alpha-thal) patients and 28 normal persons from Southern China, where the main causes of alpha-thal are three large deletions (-alpha3.7, -alpha4.2, and --SEA) and two point mutations in the alpha-globin gene cluster on chromosome 16. The results, detected by the P140B HBA kit, were in complete concordance with the results detected by multiplex polmymerase chain reaction (m-PCR) and real-time PCR. The advantages and limitations of the techniques are discussed. We concluded that MLPA was a rapid and reliable method to determine the cause of both deletional and nondeletional alpha-thal in China.
 ...
PMID:Detection of alpha-thalassemia in China by using multiplex ligation-dependent probe amplification. 1906 34

A gold nanoparticle-filled capillary electrophoresis method combined with three multiplex polymerase chain reactions (PCRs) was established for simultaneous diagnosis of five common alpha-thalassemia deletions, including the -alpha(3.7) deletion, -alpha(4.2) deletion, Southeast Asian (--(SEA)), Filipino (--(FIL)) and Thai (--(THAI)) deletions. Gold nanoparticles (GNPs) were used as a pseudostationary phase to improve the resolution between DNA fragments in a low-viscosity polymer. To achieve the best CE separation, several parameters were evaluated for optimizing the separation conditions, including the capillary coating, the concentrations of polymer sieving matrix, the sizes and concentrations of GNPs, the buffer concentrations, and the pH. The final CE method for separating a 200-base pair (bp) DNA ladder and alpha-thalassemia deletions used a DB-17 capillary, 0.6% poly(ethylene oxide) (PEO) prepared in a mixture of GNP(32nm) solution and glycine buffer (25mM, pH 9.0) (80:20, v/v) as the sieving matrix with 1microM YO-PRO-1 for fluorescence detection; the applied voltage was -10kV (detector at anode side) and the separation temperature was 25 degrees C. Under these optimal conditions, 15 DNA fragments with sizes ranging from 0.2kb to 3.0kb were resolved within 11.5min. The RSDs of migration times were less than 2.81%. A total of 21 patients with alpha-thalassemia deletions were analyzed using this method, and all results showed good agreement with those obtained by gel electrophoresis.
 ...
PMID:Genotyping of alpha-thalassemia deletions using multiplex polymerase chain reactions and gold nanoparticle-filled capillary electrophoresis. 1912 3

The definitive diagnosis of alpha-thalassemia involves detection of a deletion of one or more alpha-globin that encode the alpha-chains of Hb (hemoglobin). To determine whether DNA analysis is indicated, screening tests such as mean corpuscular volume (MCV) and Hb typing are employed. alpha-Thalassemia often correlates with normal or low HbA2 values. Zinc protoporphyrin (ZPP) is usually high in ferropenic anemia or lead-poisoning and is normal or slightly raised in beta-thalassemia. Therefore, ZPP is currently used as a marker to discriminate between ferropenic anemia and beta-thalassemia. We investigated the diagnostic potential of ZPP < 150 micromol/mol heme in a screening strategy for alpha-thalassemia. We measured ZPP and performed DNA analysis for detecting the seven most prevalent alpha-thalassemia deletions, namely, alpha3.7, SEA, alpha20.5, alpha4.2, MED, FIL, and THAI, in the blood samples of 200 patients with MCV < 70 fL and HbA2 < or = 3.5%. Deletions were detected in 9% subjects in the ZPP > or = 150 group (n = 175) and 56% subjects in the ZPP < 150 group (n = 29); this difference was statistically significant (chi-square test, P < 0.001). We conclude that ZPP < 150 micromol/mol heme can be used in a new screening strategy for alpha-thalassemia.
 ...
PMID:Diagnostic value of zinc protoporphyrin in a screening strategy for alpha-thalassemia. 1918 79

Hemoglobin (Hb) Bart's hydrops fetalis is a fatal condition associated with homozygous alpha(0)-thalassemia. Prenatal diagnosis of the disease is usually done by gap-PCR; however, misdiagnosis can occur with allelic dropout. Diagnosis using more than one method is preferred. We describe a double-check PCR assay for accurate prenatal diagnosis. The study was conducted on 64 fetuses at risk of homozygous alpha(0)-thalassemia encountered at our routine thalassemia diagnosis laboratory. Chorionic villus sample (CVS), amniotic fluid or fetal blood specimens were obtained from pregnant women at risk and analyzed by two PCR methods. In the first method, the SEA alpha(0)-thalassemia deletion of parents and fetuses were determined by gap-PCR routinely run in our laboratory. In another method, two specific fragments located 5' to the zeta(2) gene (XbaI fragment) and the alpha(2)-globin gene (RsaI fragment) together with the gap-PCR fragment were multiply co-amplified to determine the presence or absence of normal and alpha(0)-thalassemia alleles. The molecular diagnosis of alpha(0)-thalassemia was possible in all 64 fetuses using the two PCR approaches. The final diagnoses included 13 normal, 29 unaffected heterozygote and 22 homozygote alpha(0)-thalassemia fetuses.The two PCR assays disclosed no discordant result in the diagnosis of the Hb Bart's hydrops fetalis caused by alpha(0)-thalassemia.The combined PCR assay for gap-PCR, zeta(2) XbaI and alpha(2) RsaI fragments, described here, is simple, accurate and applicable in the prenatal diagnosis of Hb Bart's hydrops fetalis in a routine setting.
 ...
PMID:Accurate prenatal diagnosis of Hb Bart's hydrops fetalis in daily practice with a double-check PCR system. 1981 7

We are reporting here the results of differential gene expression experiments comparing two siblings, a 21-yr-old male and a 19-yr-old female, with the same alpha-thalassemia genotype (-alpha(3.7)/(--SEA)) and quite different levels of Hb H in the peripheral blood (18.7 and 5%, respectively). By using mRNA differential-display reverse-transcription-PCR and suppression subtractive hybridization, two main transcripts were selected in both procedures and validated by qRT-PCR, one corresponding to the phosphatidylinositol phosphate 4-kinase type II-alpha (PIP4KIIA) gene and the other to the beta-globin gene, both over expressed in the patient with the higher percentage of Hb H. Type II PIP kinases produce phosphatidylinositol 4,5 biphosphate, a critical and pleiotropic regulatory molecule involved in diverse cellular activities, including gene expression. Our results suggest that PIP4KIIA may be one of the factors related to the regulation of the beta-globin gene expression and the different levels of Hb H in alpha-thalassemic patients.
 ...
PMID:PIP4KIIA and beta-globin: transcripts differentially expressed in reticulocytes and associated with high levels of Hb H in two siblings with Hb H disease. 1965 70

The prevailing cause of alpha-thalassemia in Southeast Asia is the presence of 3 deletion mutations in the alpha-globin genes (-SEA, -alpha(3.7) and -alpha(4.2)). Current detection methods include gap polymerase chain reaction (PCR), multiplex PCR and real-time PCR with SYBR Green 1 combined with dissociation curve analysis. To improve and simplify a previously published method that requires 4 separate reactions, a duplex PCR assay was designed to detect both the nondeletional and the -SEA alleles. This duplex PCR can successfully identify the nondeletional allele and both the -SEA carrier and homozygous genotypes. The combination of the duplex PCR and 2 gap PCRs (for detection of -alpha(3.7) and -alpha(4.2)) can diagnose all types of deletional alpha-thalassemia. Our method was validated by analysis of 195 DNA samples, the results of which were consistent with prior diagnoses. The developed assay can reliably diagnose alpha0-thalassemia and all types of deletional alpha-thalassemia. The diagnostic method is simple, rapid, accurate, automated, inexpensive and has a high throughput.
 ...
PMID:Improvement in the detection of alpha0- and deletional alpha-thalassemia by real-time PCR combined with dissociation curve analysis. 1968 85

We report three examples of chronic anaemia involving complex combinations of alpha- and beta-globin gene defects. The first case had a potential Hb H disease caused by the classic SEA/RW deletions masked by Hb E [beta26(B8)Glu-->Lys] in the homozygous state. The second had an unusual Hb H disease caused by compound heterozygosity for two different alpha2 polyadenylation site mutations masked by a beta-thalassaemia heterozygosity. The third had an intermediate alpha-thalassaemia with considerable anaemia caused by an as yet unknown polyadenylation site (AATAAA>AATAAC) mutation in combination with a common RW deletion masked by a common Hb C [beta6(A3)Glu-->Lys] heterozygosity. Diagnostic methods, genotype/phenotype correlations and the chance of overlooking these combinations during risk assessment in a multiethnic society are discussed.
 ...
PMID:alpha-thalassaemia masked by beta gene defects and a new polyadenylation site mutation on the alpha2-globin gene. 1991 9


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