Application of an expanded multiplex genotyping assay for the simultaneous detection of Hemoglobin Constant Spring and common deletional alpha-thalassemia mutations.

Abstract

Hemoglobin Constant Spring (HbCS) is the most common nondeletional alpha-thalassemia variant causing HbH disease, making its detection crucial in populations at risk. Universal newborn screening for HbH is carried out in California. Identification of alpha-thalassemia genotypes responsible for HbH and HbH-CS requires rapid, accurate and cost-effective genotyping methods suitable for population screening. We incorporated the HbCS mutation into our existing seven-plex genotyping assay for common alpha-thalassemia deletions. To assess the feasibility and diagnostic utility of this expanded multiplex gap-PCR assay, we determined genotypic frequencies of HbCS in samples referred for alpha-thalassemia testing between 1 January 2006 and 31 December 2008. During the 3-year study period, 1436 samples were genotyped for alpha-thalassemia. HbH-CS accounted for 23 (13%) of the 176 cases of HbH disease identified. In a subset of 145 newborns referred by the California NBS program with an elevated Hb Bart's level at birth, HbH disease was confirmed in 134 (93%) and HbH-CS identified in 13 (10%) of these. This expanded genotyping assay has proven to be a rapid, reliable and clinically useful diagnostic tool for the detection of HbH-CS disease.

• Authors: J L Kidd, M Azimi, B Lubin, E Vichinsky, C Hoppe
• Journal: International journal of laboratory hematology (Int J Lab Hematol) Vol. 32 Issue 4 Pg. 373-80 (Aug 01 2010) ISSN: 1751-553X [Electronic] England
• PMID: 19919622 (Publication Type: Journal Article)

Chemical References

• Hemoglobins, Abnormal
• Hemoglobin Constant Spring

Topics

• California
• Follow-Up Studies
• Genotype
• Hemoglobins, Abnormal (genetics)
• Humans
• Infant, Newborn
• Polymerase Chain Reaction (methods)
• Sequence Deletion (genetics)
• alpha-Thalassemia (blood, diagnosis, genetics)