One hundred and thirty one different hemoglobin (Hb) variants and 134 families with thalassemia syndrome were reported during 30 years search for hemoglobinopathy in Japan. Studies on their molecular pathology and gene abnormalities have elucidated the effects of base substitution in the genomic DNA. The expression of the abnormal gene products decreases in a graded manner as follows: hemoglobinopathies due to stable Hb variants----unstable Hb disorder----hyperunstable Hb disorder----thalassemic expression of Hb variants----thalassemia syndrome without abnormal gene product.
