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Test ID WGSEQ Gamma-Globin Full Gene Sequencing, Varies


Necessary Information


A complete patient history is strongly encouraged.



Specimen Required


Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA)

Acceptable:  Yellow top (ACD)

Specimen Volume: 4 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in the original tube. Do not aliquot.

Specimen Stability Information: Refrigerate 30 days(preferred)/Ambient 14 days

 

Specimen Type: Extracted DNA from whole blood

Container/Tube: 1.5 to 2 mL tube

Specimen Volume: Entire specimen

Collection Instructions: Label specimen as extracted DNA from blood and provide indication of volume and concentration of the DNA

Specimen Stability Information: Frozen (preferred)/Refrigerate/Ambient


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826)

2. Thalassemia/Hemoglobinopathy Patient Information (T358)

3. If not ordering electronically, complete, print, and send a Benign Hematology Test Request (T755) with the specimen.

Useful For

An adjunct in the interpretation of hemoglobin electrophoresis results

 

Evaluation for suspected gamma variants or nondeletional hereditary persistence of fetal hemoglobin (HPFH)

 

Assessment of unstable gamma chain variants when other tests for causes of hemolysis are unrevealing)

Method Name

Polymerase Chain Reaction (PCR) Amplification/Sanger Sequence Analysis

Reporting Name

Gamma Globin Full Gene Sequencing

Specimen Type

Varies

Specimen Minimum Volume

Blood: 1 mL
Extracted DNA: 50 mcL at 50 ng/mcL concentration

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

Clinical Information

Hemoglobin F (HbF) is the dominant hemoglobin at birth but is gradually replaced by adult hemoglobin (HbA) during the year after birth (normal value ≤1% of total hemoglobin after age 2). Increased HbF levels may continue after the neonatal period and into adulthood for various reasons. Genetic causes include deletional and nondeletional forms of hereditary persistence of fetal hemoglobin (HPFH) and delta-beta thalassemia variants. Over 100 genetic variants have been described in the gamma genes and, if detectable, the protein expression will vary over time according to the overall HbF expression. Gamma globin variants can manifest either as a quantitative (gamma thalassemia or nondeletional HPFH) or a qualitative (gamma variant) abnormality. Nondeletional HPFH alterations frequently modulate the expected severity of sickling disorders due to the inhibitory properties of HbF on sickle formation. Many gamma chain variants are benign, although some, such as unstable, high- and low-oxygen affinity, or M hemoglobin variants, cause hemolytic anemia/hyperbilirubinemia, erythrocytosis, cyanosis, and methemoglobinemia, respectively. The percentages of gamma variants will vary according to if they are present on the HBG1 or HBG2 genes, as these genes are differentially expressed depending on the age of the patient. Symptoms due to gamma variants are expected to decrease along with the normal decrease in HbF and therefore, most resolve after the first 6 months of life.

Reference Values

An interpretive report will be provided.

Interpretation

An interpretive report will be provided and will include specimen information, assay information, and whether the specimen was positive for any variants in the gene. If positive, the alteration will be correlated with clinical significance, if known.

Clinical Reference

1. Crowley MA, Mollan TL, Abdulmalik OY, et al: A hemoglobin variant associated with neonatal cyanosis and anemia. N Engl J Med. 2011 May 12;364(19):1837-1843

2. Cui J, Baysdorfer C, Azimi M, et al: Identification of three novel Hb F variants: Hb F-Hayward [Ggamma1(NA1)Gly>Asp, GGT>GAT], Hb F-Chori-I [AgammaT16(A13)Gly>Asp, GGC>GAC] and Hb F-Chori-II [AgammaI29(B11)Gly>Glu, GGA>GAA]. Hemoglobin. 2012;36:305-309

3. Akinsheye I, Alsultan A, Solovieff N, et al: Fetal hemoglobin in sickle cell anemia. Blood. 2011 Jul 7;118(1):19-27

4. Steinberg M, Forget B, Higgs D, Weatherall D, eds. Disorders of Hemoglobin Genetics, Pathophysiology, and Clinical Management. 2nd ed. Cambridge University Press; 2009

5. Provan D, Gribben J, eds. Molecular Hematology. 3rd ed. Blackwell Publishing; 2010

6. Hoyer JD, Kroft SH, eds. Color Atlas of Hemoglobin Disorders: A Compendium Based on Proficiency Testing. College of American Pathologists; 2003

7. Merchant S, Oliveira JL, Hoyer JD, Viswanatha DS: Molecular diagnosis in hematopathology. In: Goldblum J. Hsi E, eds. Hematopathology: A Volume in the Series: Foundations in Diagnostic Pathology. 2nd ed. Churchill Livingstone; 2012:chap 24

Day(s) Performed

Monday through Friday

Report Available

10 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81479-Unlisted molecular

LOINC Code Information

Test ID Test Order Name Order LOINC Value
WGSEQ Gamma Globin Full Gene Sequencing 95795-1

 

Result ID Test Result Name Result LOINC Value
46952 Gamma Globin Gene Sequencing Result 50397-9
46953 Gamma Globin Interpretation 59466-3