Severe Congenital Neutropenia
Genomics and Pathology Services (GPS) offers germline variant detection by next-generation sequencing in key genes implicated in severe congenital neutropenia.
Results can provide physicians with useful information to make more definitive diagnoses in order to better manage their patients. They also enable tailored genetic counseling in both the patient and at-risk family members.
For information about The Severe Chronic Neutropenia International Registry (SCNIR) visit their website or call 1-800-726-4463.
Indications for Testing
Indications for testing include symptoms of congenital neutropenia, a family history of neutropenia, recurrent childhood infection, osteopenia, osteoporosis, childhood leukemia, childhood MDS, recurrent fever, recurrent sinusitis and recurrent gingivitis.
48 genes sequenced include AK2, AP3B1, ASXL1, CD40LG, CLPB, CSF3R, CXCR2, CXCR4, DNAJC21, DNM2, DOCK2, EFL1, EIF2AK3, ELANE, G6PC3, GATA1, GATA2, GFI1, GINS1, HAX1, IRAK4, JAGN1, KAT6A, KRAS, LAMTOR2, LYST, MYD88, NRAS, PGM3, PSTPIP1, RAB27A, RAC2, RUNX1, SBDS, SLC37A4, SMARCD2, SRP54, STK4, TAZ, TCIRG1, TCN2, TP53, USB1, VPS13B, VPS45, WAS, WDR1 and WIPF1.
Tests are performed using targeted hybridization capture coupled with next-generation sequencing (NGS) in our CAP/CLIA labs for comprehensive coverage of all coding exons of ordered genes.
Types of variation detected include single nucleotide variants (SNVs) and small insertions and deletions (indels).
For some cases with negative results or isolated heterozygous mutations in recessive genes, additional testing by alternate methodology will be performed to determine the presence of rare variant types not detected by this assay.
Results and Interpretation
DNA sequence data are analyzed by GPS’ clinically validated bioinformatics pipeline to identify and annotate genetic variants associated with severe congenital neutropenia.
Variants are interpreted by a board-certified clinical genomicist in the context of the patient’s disease. Those that are most likely to account for the observed clinical phenotype based on evidence from the medical literature are highlighted.
Results are returned to the ordering physician in a concise report.
The turnaround time for testing and interpretation of sequencing is four to six weeks from the time a specimen arrives. If performed, deletion/duplication analysis may take an additional six weeks.
Specimen types accepted include 8 mL peripheral blood in lavender-top EDTA tubes. Specimen collection kits are available upon request.
The SCN Gene Set is designed to identify genetic mutations in individuals with symptoms consistent with Severe Congenital Neutropenia.
Many times, patients present with a variety of related phenotypes making diagnosis challenging. Targeted next-generation sequencing provides clinicians with a powerful tool to analyze multiple genes with clinical relevance to enhance the diagnostic yield of testing.
Identification of a pathogenic mutation can often be used to make a more definitive diagnosis, allowing for more appropriate patient management. It also enables tailored genetic counseling in both the patient and at-risk family members.
Over time, such analyses have the potential for genotype-phenotype correlations to be drawn and may enable disease-specific therapies.