Laotian (delta beta) degree-thalassemia: molecular characterization of a novel deletion associated with increased production of fetal hemoglobin

We have identified and molecularly characterized a novel deletion in the beta-globin gene cluster that increases fetal hemoglobin (HbF) synthesis in a 24-year-old Laotian man who is heterozygous for this mutation. The patient is asymptomatic with a mild anemia, hypochromia, and microcytosis (Ht = 39%, MCH = 22.8 pg, MCV = 71 fl), normal levels of HbA2 (3.0%) and 11.5% HbF (G gamma A gamma ratio 60 to 40), with heterocellular distribution (52% F cells). Extensive restriction endonuclease mapping defined the 5' breakpoint within the IVS II of the delta-globin gene, between positions 775 to 781 very similar to the 5' breakpoint of the Sicilian delta beta-thalassemia. However, the 3' breakpoint was localized between two Pst I sites 4.7 kb 3' of the beta- globin gene, thus ending about 0.7 kb upstream from the 3' breakpoint of the Sicilian delta beta-thalassemia. This results in a 12.5 kb deletion of DNA. It is of interest that the 5' breakpoint of the deletion residues within an AT-rich region which has been proposed as a specific recognition signal for recombination events, while the 3' breakpoint lies within a cluster of L1 repetitive sequences (formerly known as Kpn I family repeats). The presence of the 3' breakpoints of several other deletions within this region of L1 repeats also suggests that such sequences might serve as hot spots for recombination and eventually lead to thalassemia deletions. The similarity of the 5' and 3' breakpoints of these delta beta-thalassemias underscores the putative regulatory role of the deleted and juxtaposed sequences on the expression of the gamma-globin genes in adult life.     

Clinico-instrumental characteristics of the state of the myocardium of patients with long Q-T interval syndrome detected during a population survey

A comprehensive clinical and instrumental study involving the collection of complaints, resting ECG records, bicycler ergometry, Holter monitoring, echocardiography was performed in 80 Novosibirsk's residents (66 males and 14 females) aged 25-64 years who had the prolonged Q-T interval syndrome detected during a population survey. ECG frequently showed the early ventricular repolarization syndrome (23%) in males and left ventricular hypertrophy (36%) in females. Bicycle ergometry increased Q-T interval in 11% of males and decreased or unchanged it in the remaining cases. Holter monitoring revealed cardiac arrhythmias in 39% of males and 64% of females, supraventricular and monotopic ventricular premature beats being prevalent. The method was found to have advantages in detecting arrhythmias. Echocardiography performed in males made it possible to identify ventricular septum hypertrophy (40%) and mitral valve prolapse (20%). The examinees with the prolonged Q-T interval syndrome mostly had arterial hypertension, coronary heart disease, and alcoholic cardiomyopathy.