In This Section      

Cystic Fibrosis-Related Disorders NGS Panel (excludes CFTR)


Syndrome Information

Clinical Description

Mild presentations of recessive pseudohypoaldosteronism (PHA) Type 1 caused by mutations in the epithelial sodium channel genes (SCNN1ASCNN1BSCNN1G) can present with elevated sweat chloride concentration, chronic cough, and frequent lower respiratory infections. These patients do not have the more severe symptoms of either CF (severe lung disease, pancreatic insufficiency, infertility) or PHA (salt-wasting, volume depletion).

Patients with carbonic anhydrase XII deficiency caused by muations in CA12 have elevated sweat chloride concentrations. The most common presentation is severe infantile hyponatremic dehydration with hyperkalemia and failure to thrive.  Clinically asymptomatic adults have been described, and sweat chloride concentrations can be, but are not always, elevated in this subgroup of patients.

Inheritance Pattern

Autosomal Recessive

Genotype-Phenotype Correlation

Mutations in SCNN1ASCNN1B, and SCNN1G associated with residual function lead to a phenotype that has some overlap with cystic fibrosis, whereas mutations that cause complete loss of function are associated with classic presentations of severe, salt-wasting pseudohypoaldosteronism type 1 (PHA1).

No genotype-phenotype correlation is known for Carbonic anhydrase XII deficiency.

Test Information

Test Method

Next Generation Sequencing (NGS) of the coding regions and intron-exon boundaries of the listed genesDeletion/Duplication:  Dosage analysis by normalization of NGS read depth for the listed genes; Sanger sequencing for potential fill in / confirmation 

This test is also available as part of one or more NGS panels for cystic fibrosis and related disorders.

Clinical Utility

Identification of causative mutations in suspected cases of cystic fibrosis; targeted carrier testing of relatives of proband; predictive prenatal testing when familial mutations are known.   

This panel is especially useful in patients who do not have a classic presentation of cystic fibrosis and who have already had CFTR sequencing.

Clinical Sensitivity

Recessive pseudohypoaldosteronism Type 1 and carbonic anhydrase XII deficiency are rare disorders and series of patients with symptoms resembling cystic fibrosis have not been described.  

Analytic Sensitivity

> 99% for inherited single nucleotide and small insertion/deletion variants for the nucleotides evaluated; >99% for multi-exon deletions and >98% for single exon deletions; >90% for multi-exon duplications and >75% for single exon duplications. Lower limit of detection for single nucleotide variants: 25% allele frequency (>99% sensitivity).

Sample Requirements

3-6ml whole blood in EDTA (purple topped) tubes. (see Pediatric or Adult blood sample algorithms for additional information)

We prefer whole blood for all tests.

Turn Around Time

Approximately 4 weeks

Fee and CPT Codes

$2600 for routine testing on a blood sample

CPT Code: 81406 x 3; 81479

Special Considerations

Sequencing of the genes included in this panel is not recommended in the carrier screening setting.

This test is also available as part of one or more NGS panels for cystic fibrosis and related disorders.

INFORMED CONSENT from the patient is required prior to ordering a genetic test. The DNA Diagnostic Lab's consent is located on the second page of the requisition form. There is also a patient brochure, "Things Every Patient Should Know Before Consenting to a Genetic Test", available for download.