摘要:

Thirty-three Tunisian patients, homozygous for Hb S, were examined. Haplotyping using nine restriction sites in theβ-globin gene cluster revealed that the most common type is the Benin type [- - - - + - + - +] which occurs at a frequency of 0.94% (31 cases); only one patient was homozygous for an atypical haplotype which shows some differences with the Benin haplotype at sites 1, 5, 6, and 8 [+-—- + + + +]; the two remaining patients were assumed to be double heterozygotes for the Benin and atypical haplotypes. The presence of the atypical haplotype suggested a double origin of the Bsgene in Tunisia. Moreover, a heterogeneity in the Hb F production was observed, ranging between 2 to 16%, whereas theGγ-globin expression was remarkably homogeneous in our patients with a normal amount approaching 40%. These results suggested the presence of a combination of several control factors.

ISSN:0363-0269    

DOI:10.3109/03630269109072480

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

We analyzed the mutations present in 19 patients withβ-thal-assemia major, in 11 patients with Hb S-β-thalassemia, and the Bshaplotypes of 34 patients with sickle cell anemia. The study included 84 relatives. Dot-blot analysis of amplified DNA with various specific oligonucleotide probes identified 11 different knownβ-thalassemia mutations and frameshifts; a new frameshift at codons 25/26 (+T) was detected through sequencing of amplified DNA. The commonβ-thalassemia mutations at codon 39 (C→T) and at IVS-I-110 (G→A) were also most prevalent among the Tunisian patients, while the milder T→C mutation at IVS-I-6 was not found. All mutations cause a Bd`-thalassemia or a severe B+-thalassemia [T→A at -30; IVS-I-5 (G→A); IVS-I-110 (G→A)] which explains the need for regular blood transfusions in the thalassemia major and S-β-thalassemia patients. Nearly all sickle cell anemia patients carried theβsmutation on a chromosome with haplotype 19 (or Benin) and all had severe anemia with sickling complications. Identification of theβShaplotype was through dot-blot analysis with oligonucleotide probes that detect mutations in theGγandAγpromoter sequences, specific for this haplotype.

ISSN:0363-0269    

DOI:10.3109/03630269109072481

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

We describe a new deletional form ofγδβ-thalassemia segregating in two generations of a family of Irish descent. Affected family members present with aβ-thalassemia minor phenotype, normal Hb A2and Hb F levels. Genomic blotting analyses on DNA from affected family members show heterozygosity for a large deletion beginning at least 15 kb upstream of the 5′endpoint of theγδβ-thalassemia-1 deletion, extending through the entireβ-like globin gene cluster, and continuing for at least 10 kb beyond the 3′endpoint of the deletion associated with the Spanish form ofδβd`-thalassemia. This deletion is among the largest described so far, and removes at least 205 kb encompassing the entireβ-like globin gene cluster on chromosome 11.

ISSN:0363-0269    

DOI:10.3109/03630269109072482

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

Hb. Heathrow [β103(G5)Phe→Leu] was identified in an Englishman with a life-long history of polycythemia, his father had been similarly affected. A hemoglobin variant was suspected from the high oxygen affinity of the patient's blood. The Hb Heathrow abnormalβchain was resolved from the normalβchain by high performance liquid chromatography, and the abnormal peptide and the amino acid replacement were identified by mass spectrometry. The corresponding base change (C→G at codon 103) was demonstrated by sequence analysis of the polymerase chain reaction amplified exon 2 of the genomicβ-globin gene. This is only the third known instance of Hb Heathrow.

ISSN:0363-0269    

DOI:10.3109/03630269109072483

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

Hb Stanmore is a new hemoglobin variant with the amino acid substitutionβ111(G13)Val→Ala. It is unstable and has a low oxygen affinity. The propositus (of Italian nationality) is a double-heterozygote for Hb Stanmore andβ°-thalassemia.

ISSN:0363-0269    

DOI:10.3109/03630269109072484

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

We describe the occurrence of a chromosome with a G→A mutation at position +22 relative to the Cap site that was found in five patients withβ-thalassemia. All patients had a common type ofβ-thalassemia mutation on the second chromosome, namely the frameshift at codon 8 (-AA), the IVS-I-110 (G→A) and the IVS-II-1 (G→A) mutations. Theβgenes of two patients, including the 5′and 3′untranslated regions, were completely sequenced and no other mutations, except a few polymorphic sites, were observed. Dot-blot analyses failed to demonstrate this G→A mutation at +22 in nearly 400β-thalassemia chromosomes and 180 normal chromosomes. Hetero-zygotes have the features of a high Hb A2-β-thalassemia hetero-zygosity, although the hematological parameters might be less abnormal than observed in heterozygotes for the more commonβ-thalassemia mutations. The possibility has been presented suggesting that this mutation might impair the binding of mRNA to ribosomes. Another mutation in this segment of DNA, i.e. a C→G mutation at position +20, is observed exclusively on a chromosome which also carries the C→G mutation at IVS-II-745. It is postulated that the +20 C→G mutation accentuates theβ-thalassemia condition caused by the IVS-II-745 mutation; the mechanism might be similar to that suggested for the G→A at +22 mutation.

ISSN:0363-0269    

DOI:10.3109/03630269109072485

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

A method of identifyingδchain variants using relatively small volumes of blood is described. The procedure consists of the amplification of two segments of genomic DNA with two sets ofδchain specific primers and sequencing of the three exons (exons 1, 2, and 3) which are part of the amplified DNA segments. Data for threeδchain variants present in seven adult heterozy-gotes are presented.

ISSN:0363-0269    

DOI:10.3109/03630269109072486

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

摘要:

Hb Geelong [β139(H17)Asn→Asp] was detected in a German woman of Polish-Russian descent. It is an unstable variant which appears to increase the severity of a (β+-thalassemic phenotype in the propositus. The electrophoretic properties of Hb A and Hb Geelong are similar on cellulose acetate in both acidic and alkaline conditions. The electrophoretic mobility and the amino acid analysis ofβxT-14 indicated the substitution Asn→Asp atβ139. The sequence ofβXT-14 was confirmed by dansyl-Edman degradation. The slight increase observed in the P50of whole blood is not intrinsic to theβ139 substitution, but is thought to result from an increased 2,3-diphosphoglycerate level in response to anemia. No family studies were possible to investigate the mode of inheritance of eitherβ+-thalassemia or Hb Geelong in the propositus. Synthetic globin chain ratios suggest that impaired synthesis of the variant globin chain is partially responsible for the low level of Hb Geelong in peripheral blood.

ISSN:0363-0269    

DOI:10.3109/03630269109072487

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269109072488

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor

ISSN:0363-0269    

DOI:10.3109/03630269109072489

出版商:Taylor&Francis    

年代:1991

数据来源: Taylor