Assess for gamma globin gene variants resulting in neonatal hemolytic anemia, cyanosis or methemoglobinemia in symptomatic infants when other etiologies have been excluded. Assess for nondeletional hereditary persistence of fetal hemoglobin (HPFH) in individuals with elevated fetal hemoglobin. Characterize abnormal hemoglobins identified by electrophoresis suspected to represent gamma chain variants.
Polymerase Chain Reaction/Sequencing
Within 2 weeks
Lavender (K2EDTA), Pink (K2EDTA), or Yellow (ACD Solution A or B).
Transport 3 mL whole blood. (Min: 1 mL)
Ambient: 1 week; Refrigerated: 1 month; Frozen: 6 months
Background information for Gamma Globin (HBG1 and HBG2) Sequencing:
Characteristics: Variants in the gamma globin genes, HBG1 and HBG2, may occasionally result in either a quantitative defect (gamma thalassemia or nondeletional hereditary persistence of fetal hemoglobin) or a qualitative abnormality (gamma variant). Gamma variants resulting in unstable, high- and low-oxygen affinity or M hemoglobin variants may result in hemolytic anemia/hyperbilirubinemia, erythrocytosis/cyanosis, or methemoglobinemia in neonates, respectively. Clinical symptoms related to gamma globin variants commonly resolve after the first six months of life given the switch from fetal hemoglobin expression to adult hemoglobin expression.
Inheritance: Autosomal dominant.
Cause: Pathogenic germline variants in HBG1 or HBG2.
Clinical Sensitivity: Unknown. Gamma globin variants are a rare cause of neonatal hemolytic anemia, cyanosis, erythrocytosis, or methemoglobinemia.
Methodology: Long range PCR followed by nested PCR and bidirectional sequencing of all coding regions, intron-exon boundaries, and 5' proximal promoters of the HBG1 and HBG2 genes.
Analytical Sensitivity and Specificity: 99 percent.
Limitations: Diagnostic errors can occur due to rare sequence variations or repeat element insertions. Large deletions/duplications, distal regulatory region variants, deep intronic variants, and hybrid gene events will not be detected.
Compliance Statement C: For human genetic inheritable conditions and mutations. This test was developed and its performance characteristics determined by ARUP Laboratories. The U. S. Food and Drug Administration has not approved or cleared this test; however, FDA clearance or approval is not currently required for clinical use. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions.
Counseling and informed consent are recommended for genetic testing. Consent forms are available online.
|Component Test Code*||Component Chart Name||LOINC|
|3002038||Specimen HBG FGS||31208-2|
|3002039||HBG FGS Interpretation||53037-8|