Spontaneous mutation of the hemoglobin Leiden (beta 6 or 7 Glu-->0) in a Thai girl

We report a case of 12-year old Thai girl suffering from mild non-transfusion-dependent thalassemia intermedia. She is the single child in her family. On examination she looked pale; there was no hepatosplenomegaly. The Hb concentration was 9 g/dL. Hb typing and molecular mutation study revealed compound heterozygosity for HbE and Hb Leiden (alpha2beta26/7-Glu, codon 6/7-GAG). The proportion of HbE was 47% whereas that of Hb Leiden was 39%. The patient had no HbA. Hb typing of her father and mother revealed HbE trait, and no Hb Leiden was demonstrated. As the paternity test confirmed the parenthood, we assume that Hb Leiden has arisen by spontaneous mutation. A study of the beta< or= -globin gene framework by molecular cloning and subsequent DNA sequencing of the beta-globin gene in the members of the family indicated that the Hb Leiden mutation occurred on a maternal inherited chromosome. The deletion of codon 6 or 7 (-GAG) of the beta-globin gene in the patient may be due to an unequal crossing over during the mother's oogenesis.