Introduction to hemoglobin mutations
- Stanley L Schrier, MD
Stanley L Schrier, MD
- Editor-in-Chief — Hematology
- Section Editor — Myeloproliferative Disorders; Red Cell Disorders
- Professor of Medicine
- Stanford University School of Medicine
- Section Editors
- William C Mentzer, MD
William C Mentzer, MD
- Section Editor — Red Cell Disorders
- Professor of Pediatrics
- University of California, San Francisco
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
Over 1000 different mutations of the globin chains of the human hemoglobin molecule have been discovered [1,2]. They are classified according to the type of mutation (eg, insertion, deletion, base change), the affected globin subunit (eg, alpha chain, beta chain), and by the clinical and hematologic phenotype (table 1 and table 2). This topic review will present an introduction to the most common of these hemoglobin mutations.
●The hemoglobins found in normal adults (ie, hemoglobins A [adult], A2, and F [fetal]) are discussed separately. (See "Structure and function of normal hemoglobins".)
●Sickle hemoglobin (HbS) and the thalassemias are discussed in depth separately. (See "Diagnosis of sickle cell disorders" and "Clinical manifestations and diagnosis of the thalassemias".)
●Laboratory and DNA-based methods for separation and detection of hemoglobin mutations are discussed separately. (See "Methods for hemoglobin analysis and hemoglobinopathy testing".)
It has been estimated that in excess of 300,000 children are born in the world each year with a severe inherited disorder of hemoglobin (eg, the thalassemic and sickle cell disorders), and that approximately 80 percent of these births occur in low- or middle-income countries . Accordingly, these disorders are presenting an increasing global health burden. (See "Community public health issues and the thalassemic syndromes: Lessons from other countries".)
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- The Globin Gene Server is available at http://globin.cse.psu.edu/ (Accessed on September 19, 2013).
- High frequency mutations
- Low frequency mutations
- Clinical significance
- QUANTITATION OF MUTANT HEMOGLOBINS
- Assembly of the mutant hemoglobin
- - Positively charged beta chain mutants
- - Negatively charged beta chain mutants
- CLINICAL PHENOTYPES
- Normal hemoglobin electrophoretic pattern
- Abnormal hemoglobin electrophoretic patterns
- High performance liquid chromatography
- Hemoglobin S
- Hemoglobin E
- Hemoglobin C
- - Hemoglobin C Harlem
- Hemoglobin D
- Hemoglobin H
- - Inherited hemoglobin H diseases
- - Acquired hemoglobin H disease
- Other clinically significant hemoglobin mutations
- - Unstable hemoglobins
- - High oxygen affinity hemoglobins
- - Low oxygen affinity hemoglobins
- - Hemoglobin M disease
- - Hemoglobin Lepore
- - Hemoglobin Constant Spring
- - Hemoglobin O-Arab
- HEMOGLOBIN GENE DATABASE
- SOCIETY GUIDELINE LINKS