HEMOGLOBIN J-BISKRA - A NEW MILDLY UNSTABLE ALPHA-1 GENE VARIANT WITHA DELETION OF 8 RESIDUES (ALPHA-50-57, ALPHA-51-58 OR ALPHA-52-59) INCLUDING THE DISTAL HISTIDINE

Single point mutation, which accounts for 92% of the 700 known variant s, is the most frequent genetic defect responsible for abnormal haemog lobins. Small deletions (or insertions) involving from one to Eve resi dues are also observed, but in only approximately 5% of cases. The rem aining variants produce fusion or extended haemoglobins. A deletion of eight residues, which included the distal histidine and its neighbour s (alpha 50-57, alpha 51-58 or alpha 52-59), was found in Hb J-Biskra. This new alpha-chain variant was mildly unstable in vitro only and th ere was no haematological or biochemical evidence of haemolysis in the affected family members. 24 nucleotides were missing in a region of t he oil gene showing an identical sequence of eight nucleotides at both ends. Several starting points could therefore lead to the same nucleo tide and aminoacid remaining sequence. This deletion is the largest up to now reported in a haemoglobin molecule which is expressed at an al most normal level in the red blood cell. Comparison of the DNA sequenc es near to the deleted (or inserted) regions in the various haemoglobi ns carrying this type of abnormality almost always revealed the presen ce of a sequence that was hypothesized to slow down progression of the replication fork, and of repeats that may lead to possible secondary structures favouring slipped mispairing.