A Novel Polymorphism Causes A Different Restriction Pattern by RsaI in the β-Globin Gene Cluster: Application in Prenatal Diagnosis

Abstract

β-Thalassemia (β-thal) is a major health problem in Iran and the incidence of carriers is around 3–4%. The disease is caused by heterogeneous mutations in the β-globin gene and is characterized by hypochromic microcytic anemia. The human β-globin complex spans a region of 70 kb and contains over 20 restriction fragment length polymorphisms (RFLPs). At least nine RFLP markers including RsaI/β in the β-globin gene cluster have been routinely exploited for prenatal diagnosis. Here, we report a novel polymorphism upstream of the β-globin gene characterized by RsaI digestion. Sequencing of a fragment containing this area showed a nucleotide change (T>C) at position −223 upstream of the β-globin gene. This change could interfere with precise interpretation of the RsaI digestion pattern in linkage analysis and prenatal diagnosis of β-thal.

Keywords:

• β-Globin
• β-Thalassemia (β-thal)
• Restriction fragment length polymorphism (RFLP)

ACKNOWLEDGMENTS

The authors wish to thank the carrier couples and families for their cooperation and staff from the Primary Health Care clinics for referring the couples.

Declaration of Interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.