Caveolinopathy via the CAV3 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
467 CAV3$440.00 81404 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
Analytical sensitivity should be high as nearly all reported CAV3 mutations are the type expected to be detected by sequencing of genomic DNA.  Clinical sensitivity is difficult to predict because caveolinopathies are rare.  Among a cohort of 663 patients seen at an Italian neuromuscular disorders center who had a range of clinical phenotypes, seven probands with caveolin deficient muscle biopsies and CAV3 mutations were found (Fulizio et al. Hum Mutat 25:82-89, 2005). Among 905 unrelated long QT syndrome patients, four were found to have CAV3 mutations (Vatta et al. Circulation 114:2104- 2112, 2006).

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Deletion/Duplication Testing via aCGH

Test Code Test Copy GenesIndividual Gene PriceCPT Code Copy CPT Codes
600 CAV3$990.00 81479 Add to Order
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Turnaround Time

The great majority of tests are completed within 20 days.

Clinical Features
The caveolinopathies are disorders of skeletal and cardiac muscle that include limb-girdle muscular dystrophy type 1C (LGMD1C; OMIM 607801), rippling muscle disease (RMD; OMIM 606072), hypertrophic cardiomyopathy (OMIM 192600), and long-QT syndrome 9 (LQT9; OMIM 611818). Remarkable variability in expression is known and any of the phenotypes may occur in different members of the same family (Bruno et al. GeneReviews, 2007). LGMD1C is characterized by mild-to-moderate proximal muscle weakness, calf hypertrophy, and positive Gower sign with onset in the first decade of life (Minetti et al. Nat Genet 18:365–368, 1998). Serum CK levels are elevated up to 25-fold above normal and muscle biopsies reveal a dystrophic pattern with increased numbers of central nuclei and increased connective tissue (eg., Fulizio et al. Hum Mutat 25:82-89, 2005). RMD is a non-dystrophic muscle disorder characterized by mechanically-induced muscle contractions (Betz et al. Nat Genet 28:218-219, 2001). Onset of symptoms occurs in childhood and includes painful muscle stiffness, weakness, cramping, percussion-induced muscle mounding, and muscle hypertrophy. Muscle biopsies reveal increases in fiber size variability, centrally located nuclei, and mild type-1 fiber predominance (Betz et al. 2001). A single case report of hypertrophic cardiomyopathy due to a CAV3 mutation is known (Hayashi et al. Biochem Biophys Res Comm 313:178-184, 2004). CAV3 mutations are also causative for long-QT syndrome via a gain of function increase in late sodium current (Vatta et al. Circulation 114:2104-2112, 2006). Other associations with CAV3 mutations include hyperCKemia (Carbone et al. Neurology 54:1373–1376, 2000), sudden infant death syndrome (Cronk et al. Heart Rhythm 4:161-166, 2007), and distal myopathy (Tateyama et al. Neurology 58:323–325, 2002).
The caveolinopathies are most often inherited in an autosomal dominant mode with one parent of an affected child being affected. However, reports of recessive inheritance are also known (McNally et al. Hum Molec Genet 7:871-877, 1998; Kubisch et al. Ann Neurol 57:303-304, 2005; Muller et al. Neuromuscul Disord 16:432-436, 2006); although the health status of the carrier parents in these cases has not been well established. The same CAV3 mutation can cause varied clinical and histological consequences between and within families.
Testing Strategy
The muscle specific caveolin is encoded by exons 1-2 of the CAV3 gene located on chr 3p25. Testing is accomplished by amplifying the coding exons and ~10 bp of adjacent noncoding sequence, then determining the nucleotide sequence using standard dideoxy sequencing methods and a capillary electrophoresis instrument. 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
Individuals with clinical signs consistent with one of the associated phenotypes. Individuals with reduced to absent caveolin-3 immunoreactivity at the plasma membrane and abnormal dysferlin staining.


Official Gene Symbol OMIM ID
CAV3 601253
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Genetic Counselors
  • Betz, R. C., (2001). "Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease." Nat Genet 28(3): 218-9. PubMed ID: 11431690
  • Carbone, I., (2000). "Mutation in the CAV3 gene causes partial caveolin-3 deficiency and hyperCKemia." Neurology 54(6): 1373-6. PubMed ID: 10746614
  • Claudio Bruno, (2007). "Caveolinopathies."
  • Cronk, L. B., (2007). "Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3." Heart Rhythm 4(2): 161-6. PubMed ID: 17275750
  • Fulizio, L., (2005). "Molecular and muscle pathology in a series of caveolinopathy patients." Hum Mutat 25(1): 82-9. PubMed ID: 15580566
  • Hayashi, T., (2004). "Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy." Biochem Biophys Res Commun 313(1): 178-84. PubMed ID: 14672715
  • Kubisch, C., (2005). "Autosomal recessive rippling muscle disease with homozygous CAV3 mutations." Ann Neurol 57(2): 303-4. PubMed ID: 15668980
  • McNally, E. M., (1998). "Caveolin-3 in muscular dystrophy." Hum Mol Genet 7(5): 871-7. PubMed ID: 9536092
  • Minetti, C., (1998). "Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy." Nat Genet 18(4): 365-8. PubMed ID: 9537420
  • Muller, J. S., (2006). "Novel splice site mutation in the caveolin-3 gene leading to autosomal recessive limb girdle muscular dystrophy." Neuromuscul Disord 16(7): 432-6. PubMed ID: 16730439
  • Tateyama, M., (2002). "Mutation in the caveolin-3 gene causes a peculiar form of distal myopathy." Neurology 58(2): 323-5. PubMed ID: 11805270
  • Vatta, M., (2006). "Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome." Circulation 114(20): 2104-12. PubMed ID: 17060380
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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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