Familial Renal Amyloidosis: FGA Sequencing

Diagnostic Use

Familial renal amyloidosis (FRA) is a distinct form of amyloidosis that is hereditary (autosomal dominant) and predominantly affects the kidneys. Most cases of systemic amyloidosis (with renal involvement) are acquired and caused by deposition of immunoglobulin chains (primary amyloidosis, AL) or serum amyloid protein (secondary amyloidosis, AA). In the remaining cases, the disease is hereditary and of these cases, 80% will be caused by the Glu526Val mutation in exon 5 of the Fibrinogen Aα gene. Less frequently other fibrinogen Aα gene mutations (within exon 5) are involved or mutations in other genes: ApoAl; ApoAll; Lysozyme; and Cystatin C.

FRA typically manifests in mid to late adult life. The age at presentation, like other clinical features varies among mutations and even within individual kindreds. Most patients diagnosed with Fibrinogen Aα Glu526Val present in late to middle-age with proteinuria or hypertension and progress to end-stage renal failure over 5-10 years. Penetrance and clinical features can be highly variable between different families with the same mutation or even within individual kindreds.

Indications: Family history of FRA ± symptoms of renal dysfunction including proteinuria, hypotension, biopsy immunohistochemistry staining of amyloid fibrils positive with antibody against fibrinogen Aα chain or staining negative for SAA, lambda Ig chains and APOAI.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Constituent Tests

• Genomic DNA Extraction

Synonyms

FRA

Turnaround Time

4 weeks

Test Code

7312

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 test requires nucleated cells. Please do not centrifuge or freeze blood sample.
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 test requires nucleated cells. Please do not centrifuge or freeze blood sample.
If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

Exon 5 of the fibrinogen A-alpha chain gene (FGA) is amplified using PCR and analysed by DNA sequencing.

Non-Funded Test Cost

$492.72 (Exclusive of GST)

Billing Code

4570

Uncertainty of Measurement:
Automated bidirectional DNA sequencing has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

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/microlitre.

Contact Information

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