This test analyzes the ELANE gene, which is associated with ELANE-related neutropenia. ELANE-related neutropenia includes severe congenital neutropenia and cyclic neutropenia, which are primary hematologic disorders that are characterized by episodes of neutropenia and recurrent infections.
Genetic testing of these genes may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.
These genes can also be ordered as part of a broader panel. Depending on the individual’s clinical and family history, this panel may be appropriate and can be ordered at no additional charge.
Cyclic neutropenia is a rare disorder that is characterized by oscillating neutrophil counts approximately every 21 days and episodes of neutropenia that last for 3–5 days. These episodes typically begin within the first year of life. Untreated neutropenia results in fever, oral ulcerations, abdominal pain, and infection and inflammation including cellulitis, gingivitis, sinusitis, and pharyngitis/tonsillitis. Between episodes, individuals are generally healthy. Symptoms improve in adulthood. Cyclic neutropenia is not associated with an increased risk of malignancy.
Severe congenital neutropenia is non-oscillating, has low neutrophil counts, and results in more severe infections when compared to cyclic neutropenia. Omphalitis immediately after birth may often be the first symptom. Untreated individuals have features that are similar to individuals with cyclic neutropenia; diarrhea, pneumonia, and deep abscesses in the lung, liver, and subcutaneous tissues are also common. Treatment with granulocyte colony-stimulating factor (G-CSF) raises neutrophil levels and reduces complications and overall mortality from sepsis; however, several studies have shown that individuals with congenital neutropenia on long term G-CSF therapy are at an increased risk of developing myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML). One prospective study of individuals with severe congenital neutropenia found that the risk of developing MDS/AML after 15 years of G-CSF therapy was approximately 15%–25%.
Sequence analysis of the ELANE gene detects 90%–100% of mutations in individuals with cyclic neutropenia and 38%–80% of mutations in individuals with severe congenital neutropenia.
ELANE-related neutropenia is inherited in an autosomal dominant pattern. Spontaneous de novo mutations have been reported but the frequency is unknown.
Penetrance in cyclic neutropenia is complete, but clinical expression can be variable, even among affected members of a family.
Cyclic neutropenia is a rare condition affecting 1 in one million individuals worldwide. The incidence of congenital neutropenia is estimated at 1 in 200,000 individuals.
ELANE testing may be indicated for individuals who have recurrent infections, neutropenia unrelated to a syndrome, or a family history of severe congenital neutropenia or cyclic neutropenia.
If the patient has undergone a bone marrow transplant prior to genetic testing or currently has a hematological malignancy with actively circulating tumor cells, testing a sample type that is not derived from blood (such as skin biopsy) is warranted. While we do not accept this sample type directly, we can accept gDNA derived from skin or muscle, but deletion/duplication analysis is not guaranteed for gDNA samples because the success rate varies based on sample quality. Please see our Sample requirements page for more details.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|