Severe Drug-Induced Hemolysis in a Patient with Compound Heterozygosity for Hb Peterborough (: c.334G>T) and Hb Lepore-Boston-Washington (NG_000007.3: g.63632_71046del).

Unstable hemoglobins (Hbs) are often overlooked in the differential diagnoses of drug-induced hemolysis. Hb Peterborough [β111(G13)Val→Phe; : c.334G>T] is a rare unstable Hb variant, predominantly found in individuals of Italian descent, due to a structural defect involving a single amino acid substitution (phenylalanine for valine at position 111 of the β-globin chain).

Ten Years of Routine α- and β-Globin Gene Sequencing in UK Hemoglobinopathy Referrals Reveals 60 Novel Mutations.

We review and report here the genotypes and phenotypes of 60 novel thalassemia and abnormal hemoglobin (Hb) mutations discovered following the adoption of routine DNA sequencing of both α- and β-globin genes for all UK hemoglobinopathy samples referred for molecular investigation. This screening strategy over the last 10 years has revealed a total of 11 new β chain variants, 15 α chain variants, 19 β-thalassemia (β-thal) mutations and 15 α(+)-thalassemia (α(+)-thal) mutations. The large number of new thalassemia alleles confirms the wide racial heterogeneity of mutations in the UK immigrant population.

Impact of isolated germline JAK2V617I mutation on human hematopoiesis.

The association between somatic JAK2 mutation and myeloproliferative neoplasms (MPNs) is now well established. However, because JAK2 mutations are associated with heterogeneous clinical phenotypes and often occur as secondary genetic events, some aspects of JAK2 mutation biology remain to be understood. We recently described a germline JAK2V617I mutation in a family with hereditary thrombocytosis and herein characterize the hematopoietic and signaling impact of JAK2V617I.

Prenatal diagnosis of hemoglobinopathies by pyrosequencing: a more sensitive and rapid approach to fetal genotyping.

Prenatal diagnosis of the hemoglobinopathies by fetal DNA analysis is currently performed in most countries, either by DNA sequencing, restriction enzyme polymerase chain reaction (RE-PCR) or the amplification refractory mutation system (ARMS). These methods are time consuming and prolong the turnaround time for diagnosis. We here describe a method utilizing pyrosequencing for the prenatal diagnosis of 12 common nondeletional α- and β-globin gene mutations in the UK population.

Sick leave in the emergency department: staff attitudes and the impact of job designation and psychosocial work conditions.

Aim: To examine patterns of, and attitudes to, sick leave taken by ED and other hospital staff and to compare ED doctor and nurse psychosocial work conditions.

Methods: This was an observational study in a tertiary referral ED. An audit of sick leave taken over a 2-year period (2007-2008) by all ED, general medicine (GM) and pharmacy pay groups was undertaken.

A large deletion in the human alpha-globin cluster caused by a replication error is associated with an unexpectedly mild phenotype.

We have characterized a newly identified 16.6 kb deletion which removes a significant proportion of the human alpha-globin cluster including the psizeta1, alpha(D), psialpha1 and alpha2-globin genes but leaves the duplicated alpha1 gene intact. This complicated rearrangement results from a combination of slippage and strand switching at sites of microhomology during replication.

Hb Bart's in cord blood: an accurate indicator of alpha-thalassemia.

We quantified Hb Bart's (gamma4) levels by high performance liquid chromatography (HPLC) in 103 fresh cord blood samples from Homerton Hospital, East London, UK. The alpha-globin gene arrangement was determined by Southern blot hybridization and genomic sequence analysis of the alpha-globin genes. The cord blood Hb Bart's levels ranged from 0.

Beta-thalassaemia intermedia in Lebanon.

Approximately one third of thalassaemia patients on record in Lebanon have thalassaemia intermedia. We have analysed three factors in a panel of 73 patients with this less severe form of the disease in our population: mild beta-globin gene mutations, deletions in the alpha-globin gene and the presence of a polymorphism for the enzyme Xmn I in the Ggamma-promoter region. The results show that the most important contributing factor is the beta-genotype: 68% of patients have a mild beta+ mutation (IVSI-6, cd29, -88 or -87), while 26% of patients are positive for the Xmn I polymorphism associated with increased production of HbF, which showed strong linkage to particular mutations (IVSII-1, cd8 and cd30).

Alpha-thalassaemia and globin gene rearrangements in French Polynesia.

The prevalence of alpha-thalassaemia and various globin gene rearrangements was determined in 1992 individuals living on 11 islands in French Polynesia. The gene frequencies for alpha(+)-thalassaemia (almost exclusively the -alpha 3.7III deletion form) range from 5.