Familial Amyloidosis (Finnish Type) via the GSN Gene

  • Summary and Pricing
  • Clinical Features and Genetics
  • Citations
  • Methods
  • Ordering/Specimens
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Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
1409 GSN$1020.00 81479 Add to Order
Targeted Testing

For ordering targeted known variants, please proceed to our Targeted Variants landing page.

Turnaround Time

The great majority of tests are completed within 18 days.

Clinical Sensitivity

Hereditary or familial amyloidosis occurs due to mutations in several genes. While mutations in the transthyretin (TTR) gene are the most common, accounting for ~90% of hereditary (familial) amyloidosis, about 20 mutations have been identified in the GSN gene in individuals with amyloidosis. Our full gene sequencing test is expected to detect >99% of GSN causative mutations.

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 GSN$690.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 28 days.

Clinical Features

Amyloidosis is characterized by abnormal deposition of insoluble beta-pleated sheet aggregates (amyloid) of specific plasma proteins, resulting in disruption of organ and tissue function. Deposition can be localized or systemic, be restricted to a single organ or involve multiple organs respectively. The kidney is frequently affected. Clinically, the presence of proteinuria, renal insufficiency, heart failure, orthostatic hypertension, peripheral neuropathy or unexplained kidney, heart or systemic disease are suspicious for amyloidosis (Picken 2010). Presentation includes a spectrum of symptoms varying from asymptomatic to fatigue, extremity edema, angina or syncope, which is associated with more advanced disease (Leung N. et al. 2012).

The Finnish type of familial systemic amyloidosis (FAF) or hereditary geloslin amyloidosis (HGA) caused by variants in the gelsolin gene is characterized clinically by a unique constellation of features including corneal lattice dystrophy, cranial neuropathy, bulbar signs, and skin changes. Some patients may develop peripheral neuropathy and renal failure (Sethi etal. 2013). The first sign of FAF, which often presents in the third decade of life, is corneal lattice dystrophy resulting from gelsolin amyloid deposition in the eye (Meretoja J. 1973). As the disease progresses, amyloid begins to affect the cranial and peripheral nerves, causing a slowly progressive polyneuropathy (Solomon et al. 2012). Gelsolin amyloid also deposits in the basement membrane of the skin, resulting in dermatologic abnormalities, including cutis laxa, or thickened and loosened skin with reduced elasticity and resilience (Kiuru-Enari et al. 2005).


The majority of amyloidosis is somatic in nature, involving deposition of immunoglobulin light chain (AL) as in myeloma or monoclonal gammopathies, or serum amyloid protein (AA) in chronic inflammation. However, a substantial minority of cases are due to inherited changes in amyloidogenic proteins. (Picken 2010).

Hereditary or familial amyloidosis is a rare autosomal dominant condition that occurs due to heterozygous mutations in several genes, including GSN, which was first described in 1969 by the Finnish ophthalmologist Jouko Meretoja. The estimated number of disease carriers in Finland is almost 1000, and the disease has subsequently been found in many other countries as well. The gelsolin gene is alternatively spliced to form cytoplasmic and secreted variants, and  the amyloidogenic fragments derive from aberrant processing of only the secreted form of gelsolin, also known as plasma gelsolin (Kangas et al. 2002). Both forms of the gelsolin protein attach to actin, helping assemble or disassemble actin filaments. It is thought that, through this function, the gelsolin protein regulates the formation of the actin cytoskeleton.

Hereditary geloslin amyloidosis (HGA) is primarily caused by a G654A or G654T mutation in GSN (Kiuru-Enari et al. 2013), changing the aspartate at position 187 to either an asparagine or tyrosine (legacy nomenclature). A recent report has identified a new variant of gelsolin, changing the glycine at position 167 to arginine (legacy nomenclature), resulting in renal amyloidosis (Sethi et al. 2013). The gelsolin gene defect causes expression of variant gelsolin, followed by systemic deposition of gelsolin amyloid (AGel).

Testing Strategy

This test involves bidirectional Sanger sequencing using genomic DNA of all coding exons of the GSN gene plus ~10 bp of flanking non-coding DNA on each side. We will also sequence any single exon (Test #100) in family members of patients with a known mutation or to confirm research results.

Indications for Test

Molecular genetic testing for GSN mediated amyloidosis should be considered in individuals with any of the following findings: family history of gelsolin mediated amyloidosis, presence of lattice corneal dystrophy, where biopsied tissues confirm amyloid deposition by Congo red staining which demonstrates a characteristic apple-green birefringence under polarized light, or GSN protein detection using either using immunohistochemical staining of an affected tissue biopsy or liquid chromatography and tandem mass spectrometry of tryptic digests of micro-dissected amyloid plaques (Sethi et al. 2013).


Official Gene Symbol OMIM ID
GSN 137350
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Amyloidosis, Finnish Type 105120


Genetic Counselors
  • Human Gene Mutation Database (Bio-base).
  • Kangas H, Seidah NG, Paunio T. 2002. Role of proprotein convertases in the pathogenic processing of the amyloidosis-associated form of secretory gelsolin. Amyloid 9: 83–87. PubMed ID: 12440480
  • Kiuru-Enari S, Haltia M. 2013. Hereditary gelsolin amyloidosis. Handb Clin Neurol 115: 659–681. PubMed ID: 23931809
  • Kiuru-Enari S, Keski-Oja J, Haltia M. 2005. Cutis laxa in hereditary gelsolin amyloidosis. Br. J. Dermatol. 152: 250–257. PubMed ID: 15727635
  • Leung N, Nasr SH, Sethi S. 2012. How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing. Blood 120: 3206–3213. PubMed ID: 22948045
  • Meretoja J. 1973. Genetic aspects of familial amyloidosis with corneal lattice dystrophy and cranial neuropathy. Clin. Genet. 4: 173–185. PubMed ID: 4543600
  • Picken MM. 2010. Amyloidosis-where are we now and where are we heading? Archives of pathology & laboratory medicine 134: 545–551. PubMed ID: 20367306
  • Sethi S, Theis JD, Quint P, Maierhofer W, Kurtin PJ, Dogan A, Highsmith EW. 2013. Renal Amyloidosis Associated With a Novel Sequence Variant of Gelsolin. American Journal of Kidney Diseases 61: 161–166. PubMed ID: 22938848
  • Solomon JP, Page LJ, Balch WE, Kelly JW. 2012. Gelsolin amyloidosis: genetics, biochemistry, pathology and possible strategies for therapeutic intervention. Critical Reviews in Biochemistry and Molecular Biology 47: 282–296. PubMed ID: 22360545
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Bi-Directional Sanger Sequencing

Test Procedure

Nomenclature for sequence variants was from the Human Genome Variation Society (  As required, DNA is extracted from the patient specimen.  PCR is used to amplify the indicated exons plus additional flanking non-coding sequence.  After cleaning of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit.  Products are resolved by electrophoresis on an ABI 3730xl capillary sequencer.  In most cases, sequencing is performed in both forward and reverse directions; in some cases, sequencing is performed twice in either the forward or reverse directions.  In nearly all cases, the full coding region of each exon as well as 10 bases of non-coding DNA flanking the exon are sequenced.

Analytical Validity

As of February 2018, we compared 26.8 Mb of Sanger DNA sequence generated at PreventionGenetics to NextGen sequence generated in other labs. We detected only 4 errors in our Sanger sequences, and these were all due to allele dropout during PCR. For Proficiency Testing, both external and internal, in the 14 years of our lab operation we have Sanger sequenced roughly 14,300 PCR amplicons. Only one error has been identified, and this was an error in analysis of sequence data.

Our Sanger sequencing is capable of detecting virtually all nucleotide substitutions within the PCR amplicons. Similarly, we detect essentially all heterozygous or homozygous deletions within the amplicons. Homozygous deletions which overlap one or more PCR primer annealing sites are detectable as PCR failure. Heterozygous deletions which overlap one or more PCR primer annealing sites are usually not detected (see Analytical Limitations). All heterozygous insertions within the amplicons up to about 100 nucleotides in length appear to be detectable. Larger heterozygous insertions may not be detected. All homozygous insertions within the amplicons up to about 300 nucleotides in length appear to be detectable. Larger homozygous insertions may masquerade as homozygous deletions (PCR failure).

Analytical Limitations

In exons where our sequencing did not reveal any variation between the two alleles, we cannot be certain that we were able to PCR amplify both of the patient’s alleles. Occasionally, a patient may carry an allele which does not amplify, due for example to a deletion or a large insertion. In these cases, the report contains no information about the second allele.

Similarly, our sequencing tests have almost no power to detect duplications, triplications, etc. of the gene sequences.

In most cases, only the indicated exons and roughly 10 bp of flanking non-coding sequence on each side are analyzed. Test reports contain little or no information about other portions of the gene, including many regulatory regions.

In nearly all cases, we are unable to determine the phase of sequence variants. In particular, when we find two likely causative mutations for recessive disorders, we cannot be certain that the mutations are on different alleles.

Our ability to detect minor sequence variants, due for example to somatic mosaicism is limited. Sequence variants that are present in less than 50% of the patient’s nucleated cells may not be detected.

Runs of mononucleotide repeats (eg (A)n or (T)n) with n >8 in the reference sequence are generally not analyzed because of strand slippage during PCR and cycle sequencing.

Unless otherwise indicated, the sequence data that we report are based on DNA isolated from a specific tissue (usually leukocytes). Test reports contain no information about gene sequences in other tissues.

Deletion/Duplication Testing via Array Comparative Genomic Hybridization

Test Procedure

Equal amounts of genomic DNA from the patient and a gender matched reference sample are amplified and labeled with Cy3 and Cy5 dyes, respectively. To prevent any sample cross contamination, a unique sample tracking control is added into each patient sample. Each labeled patient product is then purified, quantified, and combined with the same amount of reference product. The combined sample is loaded onto the designed array and hybridized for at least 22-42 hours at 65°C. Arrays are then washed and scanned immediately with 2.5 µM resolution. Only data for the gene(s) of interest for each patient are extracted and analyzed.

Analytical Validity

PreventionGenetics' high density gene-centric custom designed aCGH enables the detection of relatively small deletions and duplications within a single exon of a given gene or deletions and duplications encompassing the entire gene. PreventionGenetics has established and verified this test's accuracy and precision.

Analytical Limitations

Our dense probe coverage may allow detection of deletions/duplications down to 100 bp; however due to limitations and probe spacing this cannot be guaranteed across all exons of all genes. Therefore, some copy number changes smaller than 100-300 bp within a targeted large exon may not be detected by our array.

This array may not detect deletions and duplications present at low levels of mosaicism or those present in genes that have pseudogene copies or repeats elsewhere in the genome.

aCGH will not detect balanced translocations, inversions, or point mutations that may be responsible for the clinical phenotype.

Breakpoints, if occurring outside the targeted gene, may be hard to define.

The sensitivity of this assay may be reduced when DNA is extracted by an outside laboratory.

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Ordering Options

myPrevent - Online Ordering
  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.


(Delivery accepted Monday - Saturday)

  • Collect 3 ml -5 ml (5 ml preferred) of whole blood in EDTA (purple top tube) or ACD (yellow top tube). For Test #500-DNA Banking only, collect 10 ml -20 ml of whole blood.
  • For small babies, we require a minimum of 1 ml of blood.
  • Only one blood tube is required for multiple tests.
  • Ship blood tubes at room temperature in an insulated container. Do not freeze blood.
  • During hot weather, include a frozen ice pack in the shipping container. Place a paper towel or other thin material between the ice pack and the blood tube.
  • In cold weather, include an unfrozen ice pack in the shipping container as insulation.
  • At room temperature, blood specimen is stable for up to 48 hours.
  • If refrigerated, blood specimen is stable for up to one week.
  • Label the tube with the patient name, date of birth and/or ID number.


(Delivery accepted Monday - Saturday)

  • Send in screw cap tube at least 5 µg -10 µg of purified DNA at a concentration of at least 20 µg/ml for NGS and Sanger tests and at least 5 µg of purified DNA at a concentration of at least 100 µg/ml for gene-centric aCGH, MLPA, and CMA tests, minimum 2 µg for limited specimens.
  • For requests requiring more than one test, send an additional 5 µg DNA per test ordered when possible.
  • DNA may be shipped at room temperature.
  • Label the tube with the composition of the solute, DNA concentration as well as the patient’s name, date of birth, and/or ID number.
  • We only accept genomic DNA for testing. We do NOT accept products of whole genome amplification reactions or other amplification reactions.


(Delivery preferred Monday - Thursday)

  • PreventionGenetics should be notified in advance of arrival of a cell culture.
  • Culture and send at least two T25 flasks of confluent cells.
  • Some panels may require additional flasks (dependent on size of genes, amount of Sanger sequencing required, etc.). Multiple test requests may also require additional flasks. Please contact us for details.
  • Send specimens in insulated, shatterproof container overnight.
  • Cell cultures may be shipped at room temperature or refrigerated.
  • Label the flasks with the patient name, date of birth, and/or ID number.
  • We strongly recommend maintaining a local back-up culture. We do not culture cells.
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