Molecular Basis of Hb H Disease in Southwest Iran

Abstract

Although α0-thalassemia (thal) defects are not very frequent in the Iranian population, Hb H disease does occur in the country. We have analyzed the α gene cluster of 13 patients showing the presence of Hb H to establish the molecular background of this disease in southwest Iran (Shiraz and Hormozgan provinces). Using gap-polymerase chain reaction (gap-PCR) and direct DNA sequencing we have found the − −MED-I deletion, the polyadenylation signal (poly A) mutations αT-Saudiα and αT-Turkishα, and Hb Constant Spring (Hb CS) in association with the common − α3.7 deletion. This study has revealed that: 1) at least six genotypes are responsible for Hb H disease in the area: − α3.7/− −MED-I; − α3.7/αT-Saudiα; αT-Saudiα/αT-Saudiα; αCSα/− −MED-I; − −MED-I/αT-Turkishα; and the atypical forms of Hb H disease − α3.7/αCSα. 2) The molecular background of Hb H disease in the southwest area of Iran is more similar to the Mediterranean type than to the Southeast Asian. 3) Hb Bart's hydrops fetalis syndrome and mild, intermediate or severe postnatal Hb H disease conditions can be expected, but at a relatively low incidence. 4) The diagnostic flowchart for patients with microcytic hypochromic anemia should include iron deficiency, β-thal, α+- and α0-thal analyses.