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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 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.
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PMID:Distribution of beta-thalassemia mutations in the Indian population referred to a diagnostic center. 1097 38

Clinical phenotypes associated with abnormal globin chain biosynthesis may result in thalassemia (deficient quantity) or hemolytic anemia (abnormal hemoglobins). However, the phenotypic expression of hyperunstable hemoglobin variants often includes features of thalassemia, along with variable peripheral hemolysis. Hemoglobinopathies caused by highly unstable beta-chain variants have a dominant thalassemia-like phenotype, in which carriers have a clinical expression of thalassemia intermedia, but highly unstable alpha-globin variants are usually only phenotypically apparent when they interact with other alpha-thalassemia mutations. In a child with clinical and hematological features consistent with beta-thalassemia intermedia, DNA analysis excluded any beta-globin gene mutations but characterized a novel deletion cd37(C2)Pro>0 (Hb Heraklion) in the alpha1 globin gene, in trans to a common Mediterranean nondeletion alpha-thalassemia mutation (alpha(Hph)alpha). The deletion of proline at alpha37(C2) is predicted to result in severe instability of the variant hemoglobin, which on interaction with a synthesis-deficient alpha-thalassemia mutation causes a relatively severe dyserythropoietic anemia, representing an alternative phenotype associated with highly unstable alpha-chain variants. Hb Heraklion is the fourth highly unstable alpha-globin variant that we have observed in patients from Greece and Albania. Two variants involve the alpha2-globin gene: Hb Agrinio (alpha29(B10)Leu>Pro) and Hb Adana (alpha59(E8)Gly>Asp), and two the alpha1-gene: Hb Aghia Sophia (alpha62(E11)Val>0) and (Hb Heraklion a37(C2)Pro>0). Each has been observed on interaction with a different alpha-thalassemia mutation and the phenotypes associated with these highly unstable alpha-variants are presented.
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PMID:Distinct phenotypic expression associated with a new hyperunstable alpha globin variant (Hb heraklion, alpha1cd37(C2)Pro>0): comparison to other alpha-thalassemic hemoglobinopathies. 1104 28

Hereditary persistence of fetal hemoglobin (HPFH) is one of the hemoglobinopathies in which the fetal gamma-globin genes remain active in adult life. Most HPFHs are caused by a large deletion involving a variable extent of DNA segment on the beta-globin gene cluster. We report the molecular defects associated with a deletional HPFH, which has previously been described in Cambodians and Vietnamese, in two unrelated Chinese individuals. To define the sequence around the breakpoints of the deletion, both the deletion junction fragment and the normal DNA across the breakpoints were cloned by PCR and sequenced. We found that the 5' breakpoint is located between nucleotides 986 and 987 upstream from the startpoint of the beta-globin gene, which further confirmed the Southeast Asian (SEA) HPFH deletion previously determined, whereas the 3' breakpoint, which is clarified for the first time by us, lies approximately 2.3 kb downstream from the 3' HS1 site of the beta-globin gene. It is suggested that deletions were the result of a non-homologous recombination event. Based on our novel sequence data, we designed a PCR amplification method with three primers bridging the 3' breakpoint. With this method and reverse dot blot (RDB) for detecting beta-thalassemia mutations, a Chinese family that had a 6-year-old propositus with severe thalassemia intermediate and that had requested prenatal diagnosis for the second pregnancy was found to be compound heterozygotes of HPFH defects with beta-thalassemia. The fetal genomic DNA diagnosis showed the same results as those in propositus, i.e., both of them inherited the deletion from their mother and inherited a codons 14-15 (+G) frameshift mutation causing beta-thalassemia from their father.
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PMID:Molecular characterization and PCR detection of a deletional HPFH: application to rapid prenatal diagnosis for compound heterozygotes of this defect with beta-thalassemia in a Chinese family. 1107 32

A young woman aged 21 was found to be a new carrier of Hb-Belfast: beta 15 (A 12) Trp-->Arg, and the characteristics of her hemoglobinopathy were not different from those of the four cases so far described: mild hemolysis with molecular instability of the abnormal Hb, red cells inclusion bodies, and slight alterations of some functional parameters of whole blood. On this occasion, direct DNA analysis indicated the genomic nucleotide replacement of the disease: TGG-AGG. This was inherited by the mother, originating from Bari (Apulia).
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PMID:Direct DNA analysis in a new Italian carrier of Hb-Belfast: beta 15 (A12) Trp-->Arg. 1144 85

The rare hemoglobinopathies with abnormal oxygen binding are usually characterized by erythropoietin-mediated erythrocytosis. Bare et al. first described a hemoglobinopathy with mild erythrocytosis in a 22-year-old Caucasian woman in 1976. These authors called the abnormal hemoglobin Hb York. Hb York is characterized by a mutation at the beta146 position that changes histidine into proline. A second case of Hb York was observed by Kosugi et al. in 1983. To the best of our knowledge, no further cases have been reported. We have encountered a new case of Hb York, which was detected by agar gel electrophoresis at pH 6.0. Analysis of DNA sequences revealed a CAC-->CCC mutation in codon 146. The proportion of Hb York was approximately 50%. Analysis of oxygen transport function showed a leftward shift of the sigmoidal O2-dissociation curve. P50 was reduced to 15.5 mmHg. Investigation of family members revealed Hb York in the patient's sister, two daughters and a grandson. In retrospect, the mother of the patient may also have been affected. The mode of inheritance is autosomal dominant.
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PMID:Hemoglobinopathy York [beta146 (HC3) His==>Pro]: first report of a family history. 1147 52

Analysis of the molecular basis of hemoglobinopathies provides an opportunity to define genotype-phenotype variations as well as establish the origin of mutation. The present study deals with a large cohort of 1,661 cases referred to the counseling unit and 889 individuals from random screening of the population of Tripura. Characterization of mutation in 291 cases (582 alleles) was performed by the PCR-ARMS method using genomic DNA. The haplotype of 56 beta(E) mutation-bearing chromosomes were identified by the RFLP-PCR method. Genotypes were constructed and correlated with hematological and clinical phenotypes. IVS-1nt 5 (G-->C) mutation was observed as the most frequent mutation, followed by codon 30 (G-->C). Production of HbE was significantly (P < 0.001) higher in nontransfusion-dependent Ebeta-thalassemia patients. beta(E) mutation was observed only on four haplotypes linked to framework 2. Type 2 haplotype was observed mainly from chromosomes of Tripura origin, but none from South Bengal. Homozygous E individuals with 1//1 genotype were significantly (P < 0.01) more anemic compared to individuals with 2//2 genotype. This work creates a database of hemoglobinopathy mutations for the population of Eastern India which will facilitate prenatal diagnosis and counseling. Am. J. Hum. Biol. 12:454-459, 2000. Copyright 2000 Wiley-Liss, Inc.
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PMID:Interaction of different hemoglobinopathies in Eastern India with a view to establish genotype-phenotype correlation. 1153 36

Newborn screening is an accepted public health measure to ensure that appropriate health care is provided in a timely manner to infants with hereditary/metabolic disorders. Alpha-thalassemia is a common hemoglobin (Hb) disorder, and causes Hb H (beta4) disease, and usually fatal homozygous alpha(0)-thalassemia, also known as Hb Bart's (gamma4) hydrops fetalis syndrome. In 1996, the State of California began to investigate the feasibility of universal newborn screening for Hb H disease. Initial screening was done on blood samples obtained by heel pricks from newborns, and stored as dried blood spots on filter paper. Hb Bart's levels were measured as fast-moving Hb by automated high-performance liquid chromatography (HPLC) identical to that currently used in newborn screening for sickle cell disease. Subsequent confirmation of Hb H disease was done by DNA-based diagnostics for alpha-globin genotyping. A criterion of 25% or more Hb Bart's as determined by HPLC detects most, if not all cases of Hb H disease, and few cases of alpha-thalassemia trait. From January, 1998, through June, 2000, 89 newborns were found to have Hb H disease. The overall prevalence for Hb H disease among all newborns in California is approximately 1 per 15,000. Implementation of this program to existing newborn hemoglobinopathy screening in populations with significant proportions of southeast Asians is recommended. The correct diagnosis would allow affected infants to be properly cared for, and would also raise awareness for the prevention of homozygous alpha(0)-thalassemia or Hb Bart's hydrops fetalis syndrome.
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PMID:Universal newborn screening for Hb H disease in California. 1155 Nov 9

Haemoglobinopathies including alpha- and beta-thalassaemia are the world's most common class of single gene disorder. Prenatal diagnosis (PND) for beta-thalassaemia has been proven to be an effective strategy for controlling the incidence of new cases and is widely used in several countries where the disease is common. Successful preimplantation genetic diagnosis (PGD) protocols for beta-thalassaemia have been introduced using restriction fragment length polymorphism (RFLP), single-stranded conformation polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE). However, contamination and allele dropout (ADO) remain an important concern for all of these strategies. In the present study two PGD protocols for detecting beta-thalassaemia mutations (codon 41-42 and IVSI-110) and one for alpha-thalassaemia (SEA mutation) have been designed and tested. These methods contain failsafe mechanisms to reduce the risk of misdiagnosis due to ADO or contamination and utilise multiplex fluorescent PCR (F-PCR). Interestingly, amplification efficiency and ADO were significantly affected by the choice of DNA polymerase and the freshness of the single cells used. The close similarity between the DNA sequences of beta-globin and delta-globin was also found to be an important issue that necessitated careful design of primers for the beta-globin gene.
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PMID:Preimplantation genetic diagnostic protocols for alpha- and beta-thalassaemias using multiplex fluorescent PCR. 1155 12

The authors describe the first successful bone marrow transplant for the treatment of hemoglobinopathy Olmsted in a boy who presented with severe transfusion-dependent hemolytic anemia and jaundice at age 4 months. He received bone marrow from an HLA-identical sibling with normal hemoglobin electrophoresis after conditioning with busulfan, cyclophosphamide, and antithymocyte globulin when he was 18 months old. The posttransplant course was uneventful. Two years after transplantation the patient has a normal hemoglobin level without evidence of hemolysis. DNA analysis shows 100% chimerism of donor cell origin, confirming full engraftment with normal hematopoietic cells.
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PMID:Allogeneic bone marrow transplantation in a child with hemoglobinopathy olmsted. 1214 96

Hemoglobin (Hb) Korle-Bu (beta73; Asp-Asn) is the most frequent of the rare beta-chain variants in the population of West Africa whereas Hb E (beta26; Glu-Lys) is common among the Southeast Asian population. We report a hitherto undescribed condition in which these two beta-chain variants co-segregate. The proband was a 19-year-old Thai pregnant woman in her second trimester of pregnancy who visited our thalassemia screening unit. Cellulose acetate electrophoresis and high-performance liquid chromatography (HPLC) analysis of Hb detected one abnormal Hb in addition to the Hb E. Analysis of DNA sequences revealed a GAT-AAT mutation at codon 73 in trans to a GAG-AAG mutation at codon 26 of the beta-globin gene. Polymerase chain reaction (PCR) analysis of the alpha-globin gene cluster of the patient detected a 3.7-kb deletional alpha-thalassemia 2. Family study identified that her mother had the same genotype and her father was a simple Hb E carrier. The hematological data of these unusual cases of hemoglobinopathy are presented and compared with a simple heterozygote for Hb Korle-Bu found in another unrelated Thai family. beta-Globin gene haplotype linked to the Thai beta(Korle-Bu) and a simple DNA assay based on allele-specific PCR for rapid diagnosis of Hb Korle-Bu are also described.
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PMID:Compound heterozygosity for Hb Korle-Bu (beta(73); Asp-Asn) and Hb E (beta(26); Glu-Lys) with a 3.7-kb deletional alpha-thalassemia in Thai patients. 1218 10


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