Test Catalog

Test Id : SCCNP

Severe Congenital and Cyclic Neutropenia Gene Panel, Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Providing a genetic evaluation for patients with a personal or family history suggestive of severe congenital neutropenia and/or cyclic neutropenia

 

Establishing a diagnosis of an inherited congenital neutropenia and, in some cases, allowing for appropriate management and surveillance for disease features based on the gene involved

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 30 genes associated with severe congenital neutropenia and cyclic neutropenia: AK2, AP3B1, AP3D1, CD40LG, CEBPE, CLPB, CSF3R, CXCR2, CXCR4, DNAJC21, EFL1, ELANE, G6PC3, GATA2, GFI1, GINS1, HAX1, JAGN1, LYST, RAC2, SBDS, SLC37A4, SMARCD2, SRP54, TAZ(TAFAZZIN), USB1, VPS13B, VPS45, WAS, and WIPF1. See Targeted Genes and Methodology Details for Severe Congenital and Cyclic Neutropenia Gene Panel and Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for severe congenital neutropenia and cyclic neutropenia.

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For skin biopsy or cultured fibroblast specimens, fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Method Name
A short description of the method used to perform the test

Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Congenital Neutropenia GenePanel

Aliases
Lists additional common names for a test, as an aid in searching

Congenital neutropenia

CSF3R

Cyclic neutropenia

ELANE

HAX1

Neutrophil elastase

Next Gen Sequencing Test

SBDS

Severe congenital neutropenia

WAS

WIPF1

X-linked severe congenital neutropenia

X-linked thrombocytopenia

NextGen Sequencing Test

Barth syndrome

Chediak-Higashi syndrome

Cohen syndrome

Dursun syndrome

ELANE deficiency

Emberger syndrome

GATA2 deficiency

Glycogen storage disease Ia

Glycogen storage disease Ib

Glycogen storage disease Ic

HAX1 deficiency

Hermansky-Pudlak syndrome 10

Hermansky-Pudlak syndrome 2

Immunodeficiency with defective neutrophil chemotaxis

Immunodeficiency, X-linked, with hyper-IgM

Kostmann syndrome

Poikiloderma with neutropenia

Reticular dysgenesis

Shwachman-Diamond syndrome

Specific granule deficiency

WHIM syndrome

Wiskott-Aldrich syndrome

X-linked myelodysplasia

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For skin biopsy or cultured fibroblast specimens, fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Specimen Type
Describes the specimen type validated for testing

Varies

Ordering Guidance

Targeted testing for familial variants (also called site-specific or known variants testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about testing option, call 800-533-1710.

Shipping Instructions

Specimen preferred to arrive within 96 hours of collection.

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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 anticoagulant

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

 

Specimen Type: Skin biopsy

Supplies: Fibroblast Biopsy Transport Media (T115)

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin.

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured fibroblast cells from a skin biopsy from another laboratory. Cultured cells from a prenatal specimen will not be accepted.

Specimen Stability Information: Ambient (preferred)/Refrigerated (<24 hours)

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Biochemical or Molecular Testing. An additional 3 to 4 weeks is required to culture fibroblasts before genetic testing can occur.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

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

3. Congenital Neutropenia, Bone Marrow Failure, Telomere Defects, and Pulmonary Fibrosis (IPF) Patient Information

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

Blood: 1 mL; Skin biopsy or cultured fibroblasts: See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Varies

Useful For
Suggests clinical disorders or settings where the test may be helpful

Providing a genetic evaluation for patients with a personal or family history suggestive of severe congenital neutropenia and/or cyclic neutropenia

 

Establishing a diagnosis of an inherited congenital neutropenia and, in some cases, allowing for appropriate management and surveillance for disease features based on the gene involved

Genetics Test Information
Provides information that may help with selection of the correct genetic test or proper submission of the test request

This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 30 genes associated with severe congenital neutropenia and cyclic neutropenia: AK2, AP3B1, AP3D1, CD40LG, CEBPE, CLPB, CSF3R, CXCR2, CXCR4, DNAJC21, EFL1, ELANE, G6PC3, GATA2, GFI1, GINS1, HAX1, JAGN1, LYST, RAC2, SBDS, SLC37A4, SMARCD2, SRP54, TAZ(TAFAZZIN), USB1, VPS13B, VPS45, WAS, and WIPF1. See Targeted Genes and Methodology Details for Severe Congenital and Cyclic Neutropenia Gene Panel and Method Description for additional details.

 

Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for severe congenital neutropenia and cyclic neutropenia.

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

For skin biopsy or cultured fibroblast specimens, fibroblast culture will be performed at an additional charge. If viable cells are not obtained, the client will be notified.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Inherited congenital neutropenia refers to a subset of primary immunodeficiencies impacting neutrophil maturation and function. The severity of the clinical manifestations in these disorders typically reflects the degree of neutropenia. Most cases of neutropenia are due to acquired (non-genetic) causes. Severe congenital neutropenia (SCN) is characterized by chronically low neutrophil count and recurrent, often life-threatening infections beginning in the first few months of life. Some individuals with SCN may also have an increased risk for myelodysplastic syndrome or acute myelogenous leukemia.(1-3) Cyclic neutropenia (CN) is characterized by periods of severe neutropenia and infections that last 3 to 5 days and recur at regular intervals.(1-5) Individuals with SCN or CN may also exhibit recurrent fevers, sinusitis, gingivitis, cellulitis, oral ulcers, colonic ulcers, and other manifestations of chronic infections.(1-5) Bone marrow biopsy on affected individuals may show arrest in myelopoiesis at the promyelocyte/myelocyte stage.(1-3)

 

The prevalence of inherited severe congenital neutropenia and cyclic neutropenia is estimated to range from 1:500,000 to 1:100,000 live births.(1-5) The genetic etiology of inherited congenital neutropenia is most commonly due to disease-causing variants in genes that play a role in neutrophil differentiation.(1) Inheritance can be autosomal recessive, autosomal dominant, or X-linked.

 

The most common causes of isolated congenital neutropenia are disease-causing variants in the ELANE and HAX1 genes, which encode neutrophil elastase and HCLS1(hematopoietic cell-specific Lyn substrate)-associated protein X-1, respectively. Autosomal dominant ELANE-related neutropenia is the most common cause of congenital neutropenia in children and may present with oral/colonic ulcers, recurrent upper and lower respiratory infections, and various infections of the soft tissue.(2,4,6) In addition, most cases of cyclic neutropenia are due to disease-causing variants in ELANE. Autosomal recessive Kostmann disease, caused by variants in the HAX1 gene, is the second most common cause of congenital neutropenia in children and presents similarly to ELANE-related neutropenia.(2,4,6) X-linked WAS-related disorders lead to a spectrum of congenital neutropenia phenotypes including Wiskott-Aldrich syndrome and X-linked congenital neutropenia.(5,6) Isolated severe congenital neutropenia may more rarely be due to disease-causing variants in several additional genes including CSF3R, CXCR2, GFI1 and WIPF1.(1,6)

 

Severe neutropenia may also be present as part of a multisystem disorder.(1) This panel assesses for many conditions in which neutropenia is seen in conjunction with extra-hematologic features, including but not limited to:

-Shwachman-Diamond syndrome, an autosomal dominant condition due to disease-causing variants in the SBDS gene, is also characterized by exocrine pancreatic dysfunction, bone abnormalities, and hematologic abnormalities.

-GATA2-deficieny (monocytopenia and mycobacterial infection [MonoMAC] syndrome), an autosomal dominant condition due to disease-causing variants in the GATA2 gene, demonstrates a wide spectrum of clinical presentations ranging from mild chronic neutropenia with monocytopenia to Emberger syndrome and predisposition to acute myeloid malignancy.

-Barth syndrome, an X-linked condition due to disease-causing variants in the TAZ gene, is also characterized cardiomyopathy, skeletal myopathy, growth delay, and distinctive facial features.

-Cohen syndrome, an autosomal recessive condition due to disease-causing variants in the VSP13B gene, is also characterized by hypotonia, developmental delays, microcephaly, failure to thrive in infancy, truncal obesity, ophthalmologic findings, joint hypermobility, a cheerful disposition, and characteristic facial features.

-WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome, an autosomal dominant condition caused by variants in the CXCR4 gene, is also characterized by hypogammaglobulinemia and susceptibility to human papillomavirus.

Reference Values
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation
Provides information to assist in interpretation of the test results

All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(7) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Clinical Correlations:

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

 

If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals.

 

To discuss the availability of additional testing options or for assistance in the interpretation of these results, contact Mayo Clinic Laboratories genetic counselors at 800-533-1710.

 

Technical Limitations:

Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. The depth of coverage may be variable for some target regions; assay performance below the minimum acceptable criteria or for failed regions will be noted. Given these limitations, negative results do not rule out the diagnosis of a genetic disorder. If a specific clinical disorder is suspected, evaluation by alternative methods can be considered.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. Confirmation of select reportable variants will be performed by alternate methodologies based on internal laboratory criteria.

 

This test is validated to detect 95% of deletions up to 75 base pairs (bp) and insertions up to 47 bp. Deletions-insertions (delins) of 40 or more bp, including mobile element insertions, may be less reliably detected than smaller delins.

 

Deletion/Duplication Analysis:

This analysis targets single and multi-exon deletions/duplications; however, in some instances, single exon resolution cannot be achieved due to isolated reduction in sequence coverage or inherent genomic complexity. Balanced structural rearrangements (such as translocations and inversions) may not be detected.

 

This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results.

 

Genes may be added or removed based on updated clinical relevance. Refer to the Targeted Genes and Methodology Details for Severe Congenital and Cyclic Neutropenia Gene Panel for the most up to date list of genes included in this test. For detailed information regarding gene specific performance and technical limitations, see Method Description or contact a laboratory genetic counselor.

 

If the patient has had an allogeneic hematopoietic stem cell transplant or a recent non-leukoreduced blood transfusion, results may be inaccurate due to the presence of donor DNA. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

 

Reclassification of Variants:

Currently, it is not standard practice for the laboratory to systematically review previously classified variants on a regular basis. The laboratory encourages health care providers to contact the laboratory at any time to learn how the classification of a particular variant may have changed over time. Due to broadening genetic knowledge, it is possible that the laboratory may discover new information of relevance to the patient. Should that occur, the laboratory may issue an amended report.

 

Variant Evaluation:

Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline.(7) Other gene-specific guidelines may also be considered. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. Variants classified as benign or likely benign are not reported.

 

Multiple in silico evaluation tools may be used to assist in the interpretation of these results. The accuracy of predictions made by in silico evaluation tools is highly dependent upon the data available for a given gene, and periodic updates to these tools may cause predictions to change over time. Results from in silico evaluation tools are interpreted with caution and professional clinical judgment.

 

Rarely, incidental or secondary findings may implicate another predisposition or presence of active disease. These findings will be carefully reviewed to determine whether they will be reported.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Skokowa J, Dale DC, Touw IP, Zeidler C, Welte K: Severe congenital neutropenias. Nat Rev Dis Primers. 2017 Jun 8;3:17032. doi:10.1038/nrdp.2017.32

2. Fadeel B, Garwicz D, Carlsson G, Sandstedt B, Nordenskjold M: Kostmann disease and other forms of severe congenital neutropenia. Acta Paediatr. 2021 Nov;110(11):2912-2920. doi:10.1111/apa.16005

3. Tayal A, Meena JP, Kaur R, et al: A novel homozygous HAX1 mutation in a child With cyclic neutropenia: A case report and review. J Pediatr Hematol Oncol. 2022 Mar 1;44(2):e420-e423. doi:10.1097/MPH.0000000000002110

4. Dale DC, Makaryan V: ELANE-related neutropenia. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2002. Updated August 23, 2018. Accessed January 19, 2023. Available at www.ncbi.nlm.nih.gov/books/NBK1533/

5. Chandra S, Bronicki L, Nagaraj CB, et al: WAS-related disorders. In: Adam MP, Everman DB, Mirzaa GM, et al, eds. GeneReviews [Internet]. University of Washington, Seattle; 2004. Updated September 22, 2016. Accessed January 19, 2023. Available at https://www.ncbi.nlm.nih.gov/books/NBK1178/

6. Tangye SG, Al-Herz W, Bousfiha A, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022 Oct:42(7):1473-1507. doi: 10.1007/s10875-022-01289-3

7. Richards S, Aziz N, Bale S, et al; ACMG Laboratory Quality Assurance Committee: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015 May;17(5):405-424

Method Description
Describes how the test is performed and provides a method-specific reference

Next-generation sequencing (NGS) and/or Sanger sequencing are performed to test for the presence of variants in coding regions and intron/exon boundaries of the genes analyzed, as well as some other regions that have known disease-causing variants. The human genome reference GRCh37/hg19 build was used for sequence read alignment. At least 99% of the bases are covered at a read depth over 30X. Sensitivity is estimated at above 99% for single nucleotide variants, above 94% for deletions/insertions (delins) less than 40 base pairs (bp), and above 95% for deletions up to 75 bp and insertions up to 47 bp. NGS and/or a polymerase chain reaction-based quantitative method is performed to test for the presence of deletions and duplications in the genes analyzed.

 

There may be regions of genes that cannot be effectively evaluated by sequencing or deletion and duplication analysis as a result of technical limitations of the assay, including regions of homology, high guanine-cytosine (GC) content, and repetitive sequences. See Targeted Genes and Methodology Details for Severe Congenital and Cyclic Neutropenia Gene Panel for details regarding the targeted genes analyzed for each test and specific gene regions not routinely covered.(Unpublished Mayo method)

 

Confirmation of select reportable variants may be performed by alternate methodologies based on internal laboratory criteria.

 

Genes analyzed: AK2, AP3B1, AP3D1, CD40LG, CEBPE, CLPB, CSF3R, CXCR2, CXCR4, DNAJC21, EFL1, ELANE, G6PC3, GATA2, GFI1, GINS1, HAX1, JAGN1, LYST, RAC2, SBDS, SLC37A4, SMARCD2, SRP54, TAZ(TAFAZZIN), USB1, VPS13B, VPS45, WAS, and WIPF1

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

Supplemental

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Varies

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

28 to 42 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Whole blood: 2 weeks (if available); Extracted DNA: 3 months; Cultured fibroblasts, skin biopsy: 1 month

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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.

CPT Code Information
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81443

88233- Tissue culture, skin, solid tissue biopsy (if appropriate)

88240- Cryopreservation (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
SCCNP Congenital Neutropenia GenePanel In Process
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
619873 Test Description 62364-5
619874 Specimen 31208-2
619875 Source 31208-2
619876 Result Summary 50397-9
619877 Result 82939-0
619878 Interpretation 69047-9
619879 Additional Results In Process
619880 Resources 99622-3
619881 Additional Information 48767-8
619882 Method 85069-3
619883 Genes Analyzed 82939-0
619884 Disclaimer 62364-5
619885 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | PHP Pdf | CMS Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports