Test Id : AGDD

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added at an additional charge.

For any prenatal specimen that is received, maternal cell contamination studies will be performed at an additional charge. A maternal whole blood specimen is required to perform this test.

Sequence variants, other than the alpha T-Saudi and hemoglobin constant spring alterations, are not detected by this assay. For detection of single point and other nondeletion variants, order WASEQ / Alpha Globin Gene Sequencing, Varies, if clinically indicated.

All prenatal specimens must be accompanied by a maternal or gestational carrier blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Specimen preferred to arrive within 96 hours of collection.

Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

Submit only 1 of the following specimens:

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any other anticoagulant tube

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

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

Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 14 days

Specimen Type: Saliva

Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.

Supplies: Saliva Swab Collection Kit (T786)

Specimen Volume: 1 Swab

Collection Instructions: Collect and send specimen per kit instructions.

Specimen Stability Information: Ambient 30 days

Additional Information: Due to lower concentration of DNA yielded from saliva, it is possible that additional specimen may be required to complete testing.

Prenatal Specimens

Due to its complexity, consultation with the laboratory is required for all prenatal testing; call 800-533-1710 to speak to a genetic counselor.

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information:

1. A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid. An additional 2 to 3 weeks is required to culture amniotic fluid before genetic testing can occur.

2. All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information: All prenatal specimens must be accompanied by a maternal blood specimen; order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

• Molecular Genetics: Congenital Inherited Diseases Patient Information
• Informed Consent for Genetic Testing
• Informed Consent for Genetic Testing (Spanish)

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. Molecular Genetics: Congenital Inherited Diseases Patient Information (T521)

Whole blood: 1 mL; Amniotic fluid: 10 mL

Diagnosis of alpha-thalassemia

Prenatal diagnosis of deletional alpha-thalassemia

Carrier screening for individuals from high-risk populations for alpha-thalassemia

This test is not useful for diagnosis or confirmation of beta-thalassemia or hemoglobinopathies.

This test is for genetic deletions and duplications only.

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added at an additional charge.

For any prenatal specimen that is received, maternal cell contamination studies will be performed at an additional charge. A maternal whole blood specimen is required to perform this test.

The thalassemias are a group of inherited conditions characterized by decreased synthesis of one or more of the globin chains, resulting in an imbalance in the relative amounts of the alpha and beta chains. The excess normal chains precipitate in the cell, damaging the membrane and leading to premature red blood cell destruction. Additionally, the defect in hemoglobin synthesis produces a hypochromic, microcytic anemia. The frequency of thalassemia is due to the protective advantage against malaria that it gives carriers. Consequently, thalassemias are prevalent in populations from equatorial regions in the world where malaria is endemic.

Alpha-thalassemia is caused by decreased synthesis of alpha-globin chains. Four alpha-globin genes are normally present (2 on each chromosome 16). One, 2, 3, or 4 alpha-globin genes may be deleted or, less commonly, contain variants. Deletions account for approximately 90% of disease-causing alleles in alpha thalassemia. Phenotypically, these deletions result in 4 categories of disease expression:

-Deletion of 1 alpha-chain: Silent carrier state, with a normal phenotype

-Deletion of 2 alpha-chains: Alpha-thalassemia trait (alpha-1 thalassemia), with mild hematologic changes but no major clinical difficulties

-Deletion of 3 alpha-chains: Hemoglobin H disease, which is extremely variable but usually includes anemia due to hemolysis, jaundice, and hepatosplenomegaly

-Deletion of all 4 alpha-chains: Hemoglobin Barts hydrops fetalis, and almost invariably in utero fetal demise or early after birth, if left untreated. Samples with protein effects of intrauterine transfusion are increasingly common.

Less frequently, alpha-thalassemia results from single point alterations, such as hemoglobin Constant Spring (HBA2: c.427T >C).

Alpha-thalassemia occurs in all ancestral groups but is especially common in individuals of Southeast Asian and African ancestry. It is also frequent in individuals of Mediterranean ancestry. The carrier frequency is estimated to be 1 in 20 for Southeast Asians, 1 in 30 for African Americans, and 1 in 30 to 1 in 50 for individuals of Mediterranean ancestry. Both deletional and nondeletional (caused by sequence alterations) forms of alpha-thalassemia are found in individuals with Mediterranean ancestry. Those of Arab ancestry can carry a fairly common sequence alteration, called alpha- T-Saudi. Deletions in cis (two deletions on the same chromosome) are rare in African or Mediterranean populations but are prevalent in Asian populations. Couples in which both partners carry deletions in cis are at risk of having a child with hemoglobin H disease or hemoglobin Bart hydrops fetalis syndrome.

An interpretive report will be provided.

An interpretive report will be provided.

Hemoglobin electrophoresis should usually be done prior to this test to exclude other diagnoses.

In addition to disease-related probes, the multiplex ligation-dependent probe amplification technique utilizes probes localized to other chromosomal regions as internal controls. In certain circumstances, these control probes may detect other diseases or conditions for which this test was not specifically intended. Results of the control probes are not normally reported. However, in cases where clinically relevant information is identified, the ordering physician will be informed of the result and provided with recommendations for any appropriate follow-up testing.

Rare alterations (ie, polymorphisms) exist that could lead to false-negative or false-positive results. If the results obtained do not match the clinical findings, additional testing should be considered.

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.

1. Harteveld CL, Voskamp A, Phylipsen M, et al. Nine unknown rearrangements in 16p13.3 and 11p15.4 causing alpha- and beta-thalassaemia characterized by high resolution multiplex ligation-dependent probe amplification. J Med Genet. 2005;42(12):922-931. doi:10.1136/jmg.2005.033597

2. Harteveld CL, Higgs DR. Alpha-thalassemia. Orphanet J Rare Dis. 2010;5:13. doi:10.1186/1750-1172-5-13

3. Bunn HF, Forget BG. Hemoglobin: Molecular, Genetic and Clinical Aspects. 2nd ed. WB Saunders Company; 1986

4. Weatherall DJ, Higgs DR, Clegg JB, Hill AS, Nicholls R. Heterogeneity and origins of the alpha-thalassemias. Birth Defects Origi Artic Ser. 1987;23(5A):3-14

This test is a direct variant analysis assay. Deletions and duplications within the alpha-globin locus are identified by a multiplex ligation-dependent probe amplification assay. Fifteen probes that hybridize throughout the alpha-globin locus from the HS40 promoter region through the 3'HVR region are utilized in order to maximize the information needed to map the approximate location of nearly all DNA deletions that occur. In addition, a polymerase chain reaction-based assay is used to detect the presence of the alpha-3.7 and alpha-4.2 deletions.(Schouten JP, McElgunn CJ, Waaijer R, Zwijnenburg D, Diepvens F, Pals G. Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res. 2002;30[12]:e57. doi:10.1093/nar/gnf056)

Monday, Wednesday

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• Prospective clients should contact their account representative. For assistance, contact Customer Service.

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

81269

88235-Tissue culture for amniotic fluid (if appropriate)

88240-Cryopreservation (if appropriate)

81265-Comparative analysis using Short Tandem Repeat (STR) markers; patient and comparative specimen (eg, pre-transplant recipient and donor germline testing, post-transplant non-hematopoietic recipient germline [eg, buccal swab or other germline tissue sample] and donor testing, twin zygosity testing or maternal cell contamination of fetal cells (if appropriate)