Autosomal Dominant PHA1

Pseudohypoaldosteronism Type 1 (PHA1), Autosomal Dominant
	Gene:	NR3C2; chr4q31.23

Syndrome Information
	Clinical Description:	PHA1 is a salt-wasting disease. Symptoms can include poor weight gain, failure to thrive, vomiting or dehydration. Laboratory findings include hyponatremia, hyperkalemia, elevated plasma aldosterone, and elevated plasma renin activity or direct renin concentration. This disorder is also referred to as the renal PHA. Unlike recessive PHA1, symptoms tend to improve with age and treatment is eventually stopped.
	Inheritance Pattern:	Autosomal Dominant with variable penetrance (see Special Considerations below)
	Genotype-Phenotype Correlation:	None known

Test Information
	Test Method:	Bidirectional sequencing of the coding regions and intron-exon boundaries of NR3C2
	Clinical Utility:	Identification of causative mutations in known or highly suspicious cases of dominant PHA1; distinction between PHA1 subtypes for risk assessment and prognostic information; rule-out of inherited causes of salt-wasting; targeted testing of relatives of proband; predictive prenatal testing when familial mutation is known.
	Clinical Sensitivity:	58% of patients with a clinical diagnosis of PHA type 1 and 75% of patients with a clinical diagnosis and dominant family history of PHA type 1 have been reported to have a putative pathogenic NR3C2 mutation.
	Analytic Sensitivity:	Greater than 97% for nucleotides analyzed. All reports will indicate if a certain percentage of nucleotides were not called or were analyzed in a single direction.
	Turn Around Time:	4 weeks
	Fee and CPT Codes:	$1618 for routine testing on a blood sample 83891 x 1; 83898 x 15; 83904 x 30; 83909 x 30; 83912 x 1 Please contact the lab to arrange testing for known mutations on blood or prenatal samples.

Special Considerations
	Symptoms tend to improve with age until patients become essentially asymptomatic. Adults who have mutations may have only elevated aldosterone and no history of illness; therefore, parental testing of an affected child is recommended to determine recurrence risk. An intercurrent illness and resulting volume depletion in infants may be necessary for expression of the phenotype. Heterogeneity for this disorder has been postulated.

	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.
Helpful Links
	Sample Requirements Requisition and Billing forms Clinical information on PHA1, Autosomal Dominant Link to the General Test Information page for a discussion of the uses and limitations of genetic testing Patient and Family Page for general resources on genetic testing.