Carrier screening
Inclusive screening for genetic variation
For prospective and expectant parents, identifying if their children might be at risk for a genetic condition is important for informed decision-making. Carrier screening, which is performed before pregnancy or within the first few weeks of pregnancy, can provide parents with a personalized risk assessment for having a child with certain genetic disorders.
Carrier screening Test menu
Panel testing
Mayo Clinic Laboratories offers two carrier screening panels that test for the most common inherited disorders: cystic fibrosis (CF), spinal muscular atrophy (SMA), Fragile X syndrome, and hemoglobinopathies.
Key testing
- CFSMN | Cystic Fibrosis and Spinal Muscular Atrophy Carrier Screen Panel, Varies
- Screens for more than 500 genetic variants in the CFTR gene, including the most common variants associated with CF, as well as SMN1 copy number for spinal muscular atrophy (SMA).
- CSFP | Carrier Screen, Focused Panel, Varies
- Screens for CF, SMA, Fragile X syndrome, and hemoglobinopathies, including alpha thalassemia and sickle cell anemia.
Highlights
Linda Hasadsri, M.D., Ph.D., explains carrier screening at Mayo Clinic Laboratories. Using targeted genotyping, our three focused panels evaluate genes associated with cystic fibrosis, spinal muscular atrophy, and hemoglobinopathies, to provide clear answers on reproductive risks and to guide decision-making.
Single disorder testing
For family members or reproductive partners of known carriers of common conditions, carrier screening testing can help inform medical decision-making and family planning.
Key testing
- AGDD | Alpha Globin Cluster Locus Deletion/Duplication, Varies
- Determines an individual’s number of alpha-globin chains to identify carriers of alpha-thalassemia; this deletion/duplication technology has a 90% sensitivity for identifying causative variants in this gene.
- If clinically indicated, order WASEQ/Alpha Globin Gene Sequencing, Varies for detection of single point and other nondeletion variants.
- CFMP | Cystic Fibrosis, CFTR Gene, Variant Panel, Varies
- Screens for more than 500 genetic variants in the CFTR gene, including the most common variants associated with cystic fibrosis (CF).
- Able to detect CFTR deletions and duplications.
- CYPZ | 21-Hydroxylase Gene, CYP21A2, Full Gene Analysis, Varies
- Assesses the CYP21A2 gene for diagnosis of 21-hydroxylase deficient congenital adrenal hyperplasia (CAH).
- Can be used as a follow-up to positive CAH newborn screens and/or to measure basal and adrenocorticotropic hormone- 1-24 stimulated 17-hydroxyprogesterone, androstenedione, and other adrenal steroid levels.
- Answers to common question about CYP21A2 gene testing can be found below in the FAQ section.
- FXS | Fragile X Syndrome, Molecular Analysis, Varies
- Determines number of CGG trinucleotide repeats in the 5’ UTR of the FMR1 gene located on the X chromosome.
- HBEL1 | Hemoglobin Electrophoresis Evaluation, Blood
- Identifies carriers of beta-thalassemia and hemoglobin variants, such as sickle cell, by evaluating hemoglobin (Hb) A2, HbF, and performing hemoglobin electrophoresis.
- Depending on the results of protein testing, molecular testing may be added at an additional charge to further characterize abnormalities. A comprehensive interpretation will be provided when the results are complete.
- SMNCS | Spinal Muscular Atrophy Carrier Screening, Deletion/Duplication Analysis, Varies
- Determines SMN1 exon 7 copy number and SMN2 exon 7 copy number.
- Ascertains whether the g.27134T>G polymorphism is present or absent in patients found to have two copies of SMN1.
CYP21A2 frequently asked questions
Due to the complexity of the CYP21A2 gene locus, clinicians may encounter challenges in testing strategy, risk assessment, and clinical interpretation of results. Our frequently asked questions section provides guidance on the most common questions related to molecular testing of the CYP21A2 gene.
Section 1: Ordering guidance
Do you offer targeted testing for known familial variants?
No, due to the complexities of CYP21A2, we only offer full gene analysis through our test code CYPZ (21-Hydroxylase Gene, CYP21A2, Full Gene Analysis, Varies). Even if there are known CYP21A2 variants previously detected in the family, the test methodologies used in test code CYPZ allow us to fully characterize the patient’s genotype (including detection of any hybrids that can be missed on traditional carrier screening panels). Our laboratory has experience in previous cases where we have detected additional — previously undetected — reportable variants, and we are sometimes able to determine phasing of variants in patients with complex genotypes.
Are you able to accept prenatal specimens for CYPZ?
Yes, we accept chorionic villi, amniotic fluid, cultured chorionic villi, and cultured amniocytes for this test. This assay requires a large amount of high-quality DNA, which is generally not obtained from direct prenatal extractions. Therefore, our laboratory will culture any uncultured prenatal samples received. Additionally, a culturing code (either test code CULFB for cultured fibroblasts or test code CULAF for cultured amniocytes) will be added to any cultured sample received, as our laboratory maintains a culture while CYPZ testing is underway.
Can you perform prenatal testing when one or both parents have a p.Q319*+ CYP21A2 full gene duplication carrier screening result?
Yes, and in most cases, we are able to provide further resolution of the CYP21A2 genotype in the fetus. Importantly, we can generally determine if a fetus is expected to be affected with 21-hydroxylase-deficient CAH. However, if a fetus inherits the p.Q319*+ CYP21A2 full gene duplication, we may not be able to definitively determine fetal carrier status, and the report would indicate “unlikely carrier” (see section 2.2). Section 2 includes additional details on the p.Q319*+ CYP21A2 full gene duplication result.
Prenatal ordering logistics
- For specimen requirements, see the “Specimen” section in our lab test catalog.
- A maternal/gestational carrier blood specimen for maternal cell contamination studies (Mayo ID: MATCC) is strongly recommended when submitting a prenatal specimen for CYPZ testing. Maternal cell contamination studies will be performed concurrently with fetal CYP21A2 full-gene analysis.
- Due to the time-sensitive nature of prenatal testing and the complexity of the CYP21A2 locus, submitting blood samples from both biological parents (e.g., biological egg and sperm contributors) is recommended when prenatal testing is being pursued. These parental samples will be treated as controls. Having the parental samples on hand allows the laboratory (at our discretion) to perform testing on parental samples to attempt to clarify unclear fetal CYP21A2 results (for example, phasing of the detected variants) without delaying fetal results. Parental samples used as controls will be canceled after fetal testing is completed and will not have a report issued.
- If you wish to send in control specimens, you must contact the genetic counseling team ahead of specimen shipment to ensure control specimens are flagged as controls upon specimen receipt. Parental samples used as controls are not provided with a report. Control specimens received with no alert will undergo routine processing and billing as reportable samples.
| Fetal sample type | Fetal Mayo ID | Maternal Mayo ID | Paternal Mayo ID |
|---|---|---|---|
| Direct or cultured amniotic fluid | CYPZ MATCC CULAF | MATCC (blood, strongly recommended); CYPZ (blood, optional) | CYPZ (blood, optional) |
| Direct or cultured CVS | CYPZ MATCC CULFB | MATCC (blood, strongly recommended); CYPZ (blood, optional) | CYPZ (blood, optional) |
Section 2: Resulting guidance (including clarification of carrier status related to p.Q319*+duplication result)
What results can I expect from test code CYPZ?
- CYPZ is a full-gene analysis test. We perform copy number analysis to detect the number of copies of CYP21A2 and its highly homologous pseudogene, CYP21A1P. In addition, we detect hybrid or chimera alleles referred to as CYP21A2::CYP21A1P and CYP21A1P::CYP21A2.
- The CYP21A2::CYP21A1P hybrid is expected to produce an active protein unless pathogenic variants impacting 21-hydroxylase activity are detected. An individual can have the CYP21A2::CYP21A1P hybrid and still have a negative result if no reportable variants are detected.
- The hybrid CYP21A1P::CYP21A2 is an inactive hybrid and the typical byproduct of the 30kb deletion resulting from unequal crossover between CYP21A2 and CYP21A1P.
- The results section of the CYPZ report will include all results detected, including total number of copies of the gene, pseudogene, and any hybrids. The interpretation section will provide the clinical interpretation of the result.
Can test code CYPZ clarify the p.Q319*+ CYP21A2 full gene duplication result reported on carrier screening tests?
- In most instances, the detection of heterozygous p.Q319* and a full gene duplication of CYP21A2 corresponds to a known “non-carrier haplotype.” Test code CYPZ cannot definitively phase this result; however, there are two benign single nucleotide polymorphisms (SNPs) in CYP21A2 that have been reported to be associated with non-carrier status (e.g., the p.Q319* located in cis with an additional full copy of CYP21A2) for people with this result. Since test code CYPZ includes full gene sequencing of CYP21A2, we are able to detect both of these “marker SNPs.”
- If the two SNPs are present in an individual who has three copies of the CYP21A2 gene and the individual is heterozygous for p.Q319* (with no additional reportable variants detected), our laboratory will interpret this result as an “unlikely carrier.”
- However, although our testing is intended to be comprehensive and diagnostic, it is unlikely to provide definitive clarification of carrier status in people with the p.Q319*+CYP21A2 duplication genotype.
Can testing of first-degree relatives (segregation/family studies) help to clarify a p.Q319*+ CYP21A2 full gene duplication result in the setting of carrier screening?
- While rare cases exist where family studies do help to clarify carrier status, in most instances, this is not the case.
- The p.Q319*+ duplication allele is a common haplotype in the general population. Based on our laboratory’s experience and the literature, it is very unlikely that parental testing will assist in phasing a person who underwent carrier screening that detected a heterozygous p.Q319* and a CYP21A2 duplication.
- We are always willing to perform family studies; however, such studies rarely provide clarification of carrier status.