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Familial Dysautonomia via the ELP1/IKBKAP Gene - Targeted Variants Analysis

Summary and Pricing

Test Method

Bi-Directional Sanger Sequencing
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
847 ELP1 81479 81479 $440 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
847ELP181479 81479 $440 Order Options and Pricing

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Turnaround Time

12 days on average for standard orders or 8 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

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

EMAIL CONTACTS

Genetic Counselors

Geneticist

  • Greg Fischer, PhD

Clinical Features and Genetics

Clinical Features

Familial dysautonomia (FD), also known as Riley–Day syndrome and hereditary sensory autonomic neuropathy type III, is characterized by hypotonia, gastrointestinal dysfunction, vomiting crises, recurrent pneumonia, altered sensitivity to pain, taste and temperature perception, absence of fungiform papillae on the tongue, decreased or absent deep tendon reflexes, absence of overflow tears, and cardiovascular instability (Shohat and Halpern 2010). These congenital symptoms result from the abnormal development and survival of the sensory and autonomic systems, which leads to progressive neurological abnormalities FD almost exclusively occurs in individuals with Ashkenazi Jewish (AJ) ancestry. Penetrance is complete, although there is variable expressivity (Axelrod 2005). The incidence of FD among individuals with AJ heritage is 1:3600 births, and has an estimated carrier frequency of 1/30. Someone who is not of AJ ancestry has a carrier risk of less than 1:150 (Slaugenhaupt et al. 2001).

Genetics

FD is inherited in an autosomal recessive manner. It is caused by pathogenic variants in the ELP1/IKBKAP gene, which encodes a component of the Elongator complex. The complex allows for permissive chromatin structure for efficient mRNA elongation during transcription (Shohat and Halpern 2010). Two pathogenic variants account for more than 99% of affected individuals. (1) The c.2204+6T>C variant is a founder mutation that is responsible for disease in individuals with AJ heritage. It causes skipping of exon 20 resulting in a truncated IKAP protein (Dietrich et al. 2011). The abnormal transcript is tissue specific, as the abnormal transcript is found in the brain but not in lymphoblasts and fibroblasts (Slaugenhaupt et al. 2001). (2) The c.2087G>C (p.Arg696Pro) variant has been reported in the AJ population but is not as common as the intronic variant, and has not been reported in the homozygous state. Another variant c.2741C>T (p.Pro914Leu) has been reported in an individual with FD who inherited the variant from a non-AJ parent along with the common pathogenic variant from their AJ parent (Leyne et al. 2003). The missense variants appear to disrupt phosphorylation (Gold-von Simson and Axelrod 2006).

Clinical Sensitivity - Sanger Sequencing

This sequencing test will identify all previously reported pathogenic variants in the ELP1/IKBKAP gene.

Testing Strategy

The elongator complex protein 1 is encoded by 36 exons (2-37) of the ELP1/IKBKAP gene on chromosome 9q31. This test involves bidirectional Sanger sequencing using genomic DNA of selected exons /intron (exon 19, intron 20 and exon 26) for the c.2087G>C (p.Arg696Pro), c.2204+6T>C, and c.2741C>T (p.Pro914Leu) variants. We will also sequence any single exon (Test #100) in family members of patients with known mutations or to confirm research results or test only the two Ashkenazi pathogenic variants (Test #200).

Indications for Test

Candidates for this test are patients clinically diagnosed with Familial Dysautonomia or carrier testing in family members. This test is specifically designed for heritable germline mutations.

Gene

Official Gene Symbol OMIM ID
ELP1 603722
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Familial Dysautonomia AR 223900

Citations

  • Axelrod FB. 2005. Familial dysautonomia: a review of the current pharmacological treatments. Expert Opin Pharmacother 6: 561–567. PubMed ID: 15934882
  • Dietrich P, Yue J, E. S, Dragatsis I. 2011. Deletion of Exon 20 of the Familial Dysautonomia Gene Ikbkap in Mice Causes Developmental Delay, Cardiovascular Defects, and Early Embryonic Lethality. PLoS ONE 6: e27015. PubMed ID: 22046433
  • Gold-von Simson G, Axelrod FB. 2006. Familial Dysautonomia: Update and Recent Advances. Current Problems in Pediatric and Adolescent Health Care 36: 218–237. PubMed ID: 16777588
  • Leyne M, Mull J, Gill SP, Cuajungco MP, Oddoux C, Blumenfeld A, Maayan C, Gusella JF, Axelrod FB, Slaugenhaupt SA. 2003. Identification of the first non-Jewish mutation in familial Dysautonomia. American Journal of Medical Genetics 118A: 305–308. PubMed ID: 12687659
  • Shohat M, Halpern GJ. 1993. Familial Dysautonomia. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle,. PubMed ID: 20301359
  • Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L. 2001. Tissue-Specific Expression of a Splicing Mutation in the IKBKAP Gene Causes Familial Dysautonomia. The American Journal of Human Genetics 68: 598–605. PubMed ID: 11179008
  • Slaugenhaupt SA, Blumenfeld A, Gill SP, Leyne M, Mull J, Cuajungco MP, Liebert CB, Chadwick B, Idelson M, Reznik L. 2001. Tissue-Specific Expression of a Splicing Mutation in theIKBKAP Gene Causes Familial Dysautonomia. The American Journal of Human Genetics 68: 598–605.

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

View Ordering Instructions

1) Select Test Method (Backbone)


1) Select Test Type


2) Select Additional Test Options

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

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: $
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