Naxos Disease and Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia via the JUP Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
11409 JUP 81406 81406,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
11409JUP81406 81406, 81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Palmoplantar Keratoderma with Arrhythmogenic Right Ventricular Cardiomyopathy and Woolly Hair, also known as Naxos disease, is a cardiocutaneous syndrome characterized by non-epidermolytic palmoplantar keratosis, woolly hair, and the typical cardiac features of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). Usual symptoms include diffuse palmar and plantar keratosis, dense dull, bristly scalp hair, recurrent tachycardia, and palpitation. Additional symptoms include short fingers, curved nails, small hands and arms, atrial fibrillation, collapse and syncope. Naxos disease was first reported in patients from the Greek island Naxos (Protonotarios et al. Br Heart J 56:321-326, 1986). The cutaneous symptoms begin in early infancy, while the cardiac symptoms are manifested during puberty, often with syncope. Sudden death occurs in approximately 2% of patients (Protonotarios J Am Coll Cardiol 38:1477-1484, 2001). Naxos disease affects ~ 1/1000 people in the Greek islands (Protonotarios and Tsatsopoulou Cardiovasc Pathol 13:185-194, 2004).

Genetics

Naxos disease is inherited in an autosomal recessive manner. In patients of Greek origin, Naxos disease is caused by a homozygous 2 bp-deletion in the JUP gene. This deletion is defined as c.2157delTG, and causes a frameshift leading to premature protein termination (McKoy et al. Lancet 355:2119-2124, 2000). Over 90% of homozygous individuals for the c.2157delTG have electrocardiographic abnormalities; while only minor ECG changes were detected in 25% of heterozygous carriers, who are clinically unaffected (Protonotarios J Am Coll Cardiol 38:1477-1484, 2001). The 2 bp-deletion was also reported in Naxos patients of Turkish origin. Naxos disease is genetically heterogeneous, as suggested by the absence of JUP mutations in Arab families (Djabali et al. J Invest Dermatol 118:557-560, 2002). In addition to Naxos disease, heterozygous mutations in JUP are associated with autosomal dominant AVRC/D without any cutaneous abnormality (Asimaki et al. Am J Hum Genet 81:964-973, 2007; Christensen et al. J Med Genet 47:736-744, 2010).

The JUP gene encodes junction plakoglobin, an important element of cell-cell adhesion complexes.

Clinical Sensitivity - Sequencing with CNV PGxome

Sequencing of exon 12 is expected to detect mutations in all Naxos patients of Greek origin (McKoy et al. Lancet 355: 2119-2124, 2000).

Testing Strategy

This test provides full coverage of all coding exons of the JUP gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Patients with clinical features consistent with Naxos disease are candidates. Patients with Naxos disease of Greek or Turkish origin are candidates for sequencing exon 12. Patients with autosomal dominant ARVC/D are also candidates for this test. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in JUP.

Gene

Official Gene Symbol OMIM ID
JUP 173325
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Asimaki, A., et.al. (2007). "A novel dominant mutation in plakoglobin causes arrhythmogenic right ventricular cardiomyopathy." Am J Hum Genet 81(5): 964-73. PubMed ID: 17924338
  • Christensen et al. (2010) "Wide spectrum of desmosomal mutations in Danish patients with arrhythmogenic right ventricular cardiomyopathy." J Med Genet 47:736-744. PubMed ID: 20864495
  • Djabali, K., et.al. (2002). "Evidence for extensive locus heterogeneity in Naxos disease." J Invest Dermatol 118(3): 557-60. PubMed ID: 11874502
  • McKoy, G., et.al. (2000). "Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease)." Lancet 355(9221): 2119-24. PubMed ID: 10902626
  • Protonotarios, N., et.al. (1986). "Cardiac abnormalities in familial palmoplantar keratosis." Br Heart J 56(4): 321-6. PubMed ID: 2945574
  • Protonotarios, N., et.al. (2001). "Genotype-phenotype assessment in autosomal recessive arrhythmogenic right ventricular cardiomyopathy (Naxos disease) caused by a deletion in plakoglobin." J Am Coll Cardiol 38(5): 1477-84. PubMed ID: 11691526
  • Protonotarios, N., Tsatsopoulou, A. (2004). "Naxos disease and Carvajal syndrome: cardiocutaneous disorders that highlight the pathogenesis and broaden the spectrum of arrhythmogenic right ventricular cardiomyopathy." Cardiovasc Pathol 13(4): 185-94. PubMed ID: 15210133

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

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.

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.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

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