Familial Hyperaldosteronism Type 1 Genetic Analysis

Diagnostic Use

Familial hyperaldosteronism type I (FH-I) is a rare heritable, glucocorticoid remediable form of primary aldosteronism (PA) characterized by early-onset hypertension, hyperaldosteronism, variable hypokalemia, low plasma renin activity (PRA), and abnormal production of 18-oxocortisol and 18-hydroxycortisol. PA is the most common form of secondary hypertension and is found in 10% of cases. However, familial forms are rare and represent 5% of adult PA cases. FH-I is estimated at 1% of all PA cases, but may attend 3% in the hypertensive pediatric population. Hypertension, of varying severity even among members of the same family, manifests often before the age of 20. It can be accompanied with symptoms of severe hypertension such as headaches and nausea. Cardiovascular anomalies, such as fibrosis, left ventricular (LV) dysfunction, arrhythmias, and myocardial infarction, can be associated with the disease. In adults, a high risk of cerebrovascular aneurysms is observed that causes premature hemorrhagic stroke.

FH-I is due to an unequal crossing over on the long arm of chromosome 8 between the CYP11B2 gene (coding for cytochrome P450 aldosterone synthase), normally expressed in the zona glomerulosa (ZG), and the CYP11B1 gene (coding for the 11 beta-hydroxylase), normally expressed in the zona fasciculata (ZF), resulting in a chimeric gene composed of the adrenocorticotropic hormone (ACTH)-sensitive promoter of the CYP11B1 gene and the coding region of the CYP11B2gene. This leads to an excessive aldosterone synthase production in the zona fasciculata of the adrenal gland, regulated by the hypothalamo-pituitary axis rather than by the renin-angiotensin system. Excessive aldosterone synthesis leads to increased sodium reabsorption, loss of potassium and subsequent increased water reabsorption.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

CYP11B1
CYP11B2
FH-I
FHAI

Turnaround Time

4 weeks

Test Code

3878

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

4.0

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

1.0

Minimum Sample Volume (ml)

0.5

Additional Specimen Information

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Interpretation

Familial Hyperaldosteronism Type 1 (FH 1, glucocorticoid-suppressible hyperaldosteronism) represents one of the forms of human hypertension for which the precise genetic lesion is known. Unequal crossing-over between the 11beta-hydroxylase gene (CYP11B1) and the aldosterone synthase gene (CYP11B2) results in a hybrid gene which has aldosterone synthase activity, but is regulated by ACTH rather than angiotensin II.

Test Method

PCR with primers specific for the CYP11B1-CYP11B2 fusion gene, followed by agarose gel electrophoresis.

Non-Funded Test Cost

$127.91 (Exclusive of GST)

Billing Code

3878

Genomic DNA must be extracted from the specimen prior to testing. This incurs an additional charge (see GDNA). Laboratories may prefer to submit DNA for testing. Please provide a minimum of 5 micrograms of DNA at 20 nanograms / microliter.

Contact Information

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