SummaryThe association of iron deficiency anaemia, postcricoid webs and carcinoma is controversial. The main findings in a recent study which re-examined this problem are presented here. It was shown that the majority of patients with a post-cricoid web have evidence of iron deficiency but that only about 10°O of patients with iron deficiency develop post-cricoid webs. Factors which might be important in the pathogenesis of a post-cricoid web have been looked for and a few significant points noted. The main findings were an increased frequency of angular stomatitis and edentia, thyroid disease and thyroid cytoplasmic antibodies in patients with webs compared with patients with iron deficiency anaemia without a web.Follow-up studies in patients with a post-cricoid web or Paterson-Kelly syndrome show an increased frequency of post-cricoid carcinoma ranging from 4 to 16%/ in different series and the association is even more striking in patients presenting with post-cricoid carcinoma. It is concluded that the available evidence confirms the association between iron deficiency, postcricoid webs and carcinoma but the mechanism of the production of these changes is not yet understood.
Summary. Previous work involving the characterizing of a factor IX promoter mutation (¹26 G → C) of a 21-year-old patient with severe haemophilia B suggested that an androgen response element (ARE) was present in the wildtype factor IX promoter but was disrupted in this patient. However, other theories not involving this ARE have been suggested for the mechanism of recovery in the more typical (Leyden) promoter patients, so that the ARE hypothesis requires further evidence if it is to be accepted. We now present a case history and functional data on another 48-year-old severe haemophilia B patient (UK232) with a different (G → A) mutation at the same position, ¹26. This mutation impairs transactivation of the minimal factor IX promoter region (¹220 → þ43) by HNF4 in transient transfection experiments in HepG2 and HeLa cells. It disrupts binding of both androgen receptor (AR) and HNF4 to oligonucleotides spanning this region (¹40 → ¹9) in competition gel mobility shift assays. It impairs AR/ testosterone transactivation of these oligonucleotides (¹40 → ¹9) when tetramerized upstream of a CAT reporter gene in cotransfection assays in HeLa cells. And, finally, no clinical recovery has occurred since puberty. These results strengthen the evidence for the importance of nucleotide ¹26, both for the normal transcription of the gene in response to HNF4 and for the proposed Leyden recovery mechanism in response to AR and testosterone acting directly through the factor IX ARE.
Summary. We have identified three individuals of Greek or Greek Cypriot origin with an atypical form of HbH disease characterized by a severe hypochromic microcytic anaemia associated with relatively small amounts of HbH in the peripheral blood. Molecular analysis has shown that each is a compound heterozygote for a previously described mutation affecting the poly A addition signal (AATAAA→ÁTAAG) and a previously undescribed mutation involving a T→C transition in codon 29 of the α2 gene causing a leucine→pro‐line substitution. Although this mutation would be expected to produce an unstable haemoglobin and hence a haemolytic anaemia, simple heterozygotes for the α29Leu→Pro mutation have the phenotype of α‐thalassaemia trait.
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