Filipino-type β^0-thalassemia has 116 kb deletion: its correct breakpoints and five cases found in Japan

Filipino-type β-thalassemia has been reported to have about 45 kb deletion involving β-globin gene and L1 element 3'to it by Southern blot and inverse PCR analyses. However, accurate determination by Junction PCR assigned the 3' breakpoint in a New L1-like sequence far downstream from the L1, or 113 kb apart from the β-globin gene. Thus, the correct deletion is 116.4 kb instead of 45 kb. The 3' flanking region from the junction of the Filipino deletion has complete homology with the New L1-like sequence that has 80% homology with the latter half of the L1 element. The 5' brbreakpoint is exactly the same as reported in the past, and it is not related to the L1 element at all. Thus, Filipino deletion arose as an illegitimate recombination. In addition, the corrected deletion elegantly conform to the results of the past Southern blot analysis which has not been completely explained by the 45 kb deletion. We have found five unrelated cases with Filipino-type β-thalassemia in Japan where it has not been previously discovered. All cases were associated with recent immigration from Philippine, and childbearing between Filipinos and Japanese. Thus internationalization is altering the mutation spectrum of β-thalassemia in Japan. The same is noted in HbE that is endemic in the Southeast Asia.

β-thalassemia

Filipino-type

PCR

L1 element

breakpoint