Test Overview
The coding exons and associated, adjacent consensus splice sites of the PHOX2B gene are amplified using specific sets of primer pairs, and bidirectionally sequenced using fluorescently labeled chain-terminating dideoxynucleotides incorporation method (Sanger sequencing).
Analysis for the presence of pathogenic variants in PHOX2B gene (MIM: 603851) in patients with a phenotype consistent with congenital central hypoventilation syndrome (CCHS) (MIM: 209880; https://www.ncbi.nlm.nih.gov/books/NBK1427/) or neuroblastoma (with Hirschsprung disease) (NBLST2) (MIM: 613013). Sanger sequencing can detect the two major categories of PHOX2B germline variants causing CCHS or neuroblastoma: polyalanine repeat expansion mutations (PARMs, p.Ala241[24_33], 90–92%) in exon 3 polyalanine region, and non-polyalanine repeat expansion mutations (NPARMs, 8–10%) in other regions.
Interpretive report provided.
* Reference ranges may change over time. Please refer to the original patient report when evaluating results.
Sanger sequencing will not identify variants in the regulatory elements or deep intronic regions of the PHOX2B gene, and cannot detect variants in other genes associated with the clinical diagnosis. Sanger sequencing will not detect large deletions, duplications or rearrangements involving PHOX2B; specifically, it will not identify the whole gene or exon 3 deletion, a rare mechanism (<1%) for CCHS. Somatic/germline mosaicism is present in 5%-25% of asymptomatic parents, and Sanger sequencing cannot reliably detect somatic mosaicism less than 20%.
Test Details
10 days
Specimen Requirements
Restricted to Michigan Medicine in-patient orders only.
Additional Information
By ordering this test the clinician acknowledges that informed consent has been obtained from the patient as required by applicable state or federal laws and the ordering clinician has authorization from the patient permitting MLabs to report the test results to the ordering clinician. Test includes medical geneticist interpretation of results billed as a separate additional charge. This test is not available without interpretation.