THE RELATIVE LEVELS OF BETA(A) AND BETA(S) MESSENGER-RNAS IN HB-S HETEROZYGOTES AND IN PATIENTS WITH HB-S-BETA(+)-THALASSEMIA OR HB-S-BETA(+)-HPFH COMBINATIONS

We have used a quantitative reverse transcription/polymerase chain reaction (RT/PCR) procedure to evaluate the relative amounts of beta(A) and beta(S) mRNA transcripts in eight subjects with a simple Hb S heterozygosity, in six with Hb S-beta(+)-thalassaemia (thal), and in three individuals with Hb S-beta(+)-HPFH [hereditary persistence of fetal haemoglobin (Hb)] [two with the Atlanta type and one with the (G) gamma-202 (C --> G) substitution]. A balanced synthesis of beta(A) and beta(S) mRNAs was observed in all Hb S heterozygotes, whereas the beta(A) mRNA levels were reduced to similar to 16% of that of the beta(S) mRNA in the six: Hb S-beta(+)-thal compound heterozygotes, to similar to 43% in the two subjects with Hb S-beta(+)-HPFH (Atlanta type), and to 23.8% in the one individual with Hb S-beta(+)-HPFH [(G) gamma-202 (C --> G) substitution]. The higher Hb A versus Hb S levels observed in all groups of the patients studied, further confirm a post-translational control mechanism in determining the levels of Hb A and Hb S in the peripheral blood of these individuals. The procedure described here provides an accurate and easy method for studying the relative expression of particular globin genes at the transcriptional level in patients with various haemoglobinopathies.