Periodic Fever NGS Panel

Turnaround Time

5 weeks

CPT Code(s)

81479

Cost

$2,500

Genes

• CINCA syndrome
• Familial cold autoinflammatory syndrome
• Muckle-Wells syndrome
• Familial Mediterranean fever
• Periodic fever
• Mevalonic aciduria 3
• Pyogenic sterile arthritis pyoderma gangrenosum and acne (PAPA syndrome)
• Cyclic neutropenia
• Pustular psoriasis
• Majeed syndrome
• Blau syndrome
• Familial Behcet-like autoinflammatory syndrome
• Retinitis pigmentosa and erythrocytic microcytosis (RPEM)
• Sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD)

Periodic fevers are a heterogeneous group of conditions that are associated with variability in age of onset, severity, presentation, frequency, and duration of episodes. These episodes may be triggered by exposure to cold, illness or infection, stress, and overexertion. In addition to fever, common features include joint and muscle pain, rash or acne, conjunctivitis, swollen lymph nodes, abdominal pain, and pleuritis. Laboratory evidence of illness is typically present and may include increased sedimentation rate, leukocytosis, anemia, and neutropenia. Some patients experience kidney problems that can lead to kidney failure, and hepatosplenomegaly may occur. Uncommon findings limited to specific types of periodic fever can include dysmorphic features, contractures, growth abnormalities, seizures, hearing and vision loss, cardiomyopathy, and developmental delay. Most forms of periodic fever are inherited in an autosomal dominant pattern, but some appear to be autosomal recessive.

For patients with a specific suspected disorder, individual gene sequencing should be considered first. Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Next Generation Sequencing

The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.