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Congenital Insensitivity to Pain with Anhidrosis via the NTRK1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
5475 NTRK1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
5475NTRK181479 81479,81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by insensitivity to pain and inability to sweat (anhidrosis) (Indo 2008., PubMed ID: 20301726). Sweating plays important roles in maintaining normal body temperature, so anhidrosis usually leads to recurrent febrile episodes, which are often the initial manifestations of this disorder (Swanson 1963., PubMed ID: 13979626). The impaired pain sensation may not be apparent in infancy and does not draw attention to parents; therefore it usually results in repeated injuries such as oral self-mutilation, skin infection and multiple bone fractures. In general, the patients’ sensation of touch and vibration are normal (Amano et al., 1998. PubMed ID: 9798226; Kim et al. 2013., PubMed ID: 24070693).

Most patients with CIPA have some degrees of intellectual disability, including impaired conceptual thinking and abstract reasoning. Some children with CIPA also show severe attention-deficit-hyperactivity disorder (ADHD) (Levy-Erez et al., 2010. PubMed ID: 20089052).

Genetics

CIPA is inherited in an autosomal recessive (AR) manner and is caused by biallelic pathogenic variants in the NTRK1 gene. NTRK1 encodes the neurotrophic tyrosine kinase-1 receptor, which plays important roles in the development of both central and peripheral nervous system (Indo 2008. PubMed ID: 20301726). To date, different types of pathogenic variants (missense, nonsense, splicing variants and frameshift deletions) have been found in the NTRK1 gene (Human Gene Mutation Database). Only one large deletion has been documented (Huehne et al., 2008. PubMed ID: 18077166). Relatively common founder variants have been reported (Indo., 2001. PubMed ID: 11748840). For example, the variant c.1642del (p.Arg548Glyfs*104) accounts for more than 50% of CIPA cases in the Japanese population (Miura et al., 2000. PubMed ID: 10982191). The variant c.1842_1843insT (p.Pro615Serfs*12) has been found in about 89% of pathogenic NTRK1 alleles in Israeli Bedouins (Shatzky et al., 2000. PubMed ID: 10861667). A founder pathogenic variant (c.1615-1G>T) has also been identified in the Turkish population (Tüysüz et al., 2008. PubMed ID: 18322713).

In rare circumstances, a CIPA patient may inherit two defective copies of the NTRK1 gene from one parent, i.e., uniparental disomy (UPD). This type of non-Mendelian inheritance is rare, however, two cases of paternal UPD has been reported in patients with CIPA (Miura et al., 2000. PubMed ID: 11071380; Indo et al., 2001. PubMed ID: 11668614).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the NTRK1 gene account for all cases of CIPA. The clinical sensitivity of this test is expected to be very high (>99%), because it can detect all the documented pathogenic variants in this gene except for a multiexon deletion (Huehne et al., 2008. PubMed ID: 18077166; Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the NTRK1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with clinical features consistent with CIPA are candidates for this test. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NTRK1.

Gene

Official Gene Symbol OMIM ID
NTRK1 191315
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Hereditary Insensitivity To Pain With Anhidrosis AR 256800

Related Test

Name
Hereditary Sensory and Autonomic Neuropathy Panel

Citations

  • Amano et al., 1998. PubMed ID: 9798226
  • Huehne et al., 2008. PubMed ID: 18077166
  • Human Gene Mutation Database (Bio-base).
  • Indo 2001. PubMed ID: 11748840
  • Indo 2008. PubMed ID: 20301726
  • Indo et al., 2001. PubMed ID: 11668614
  • Kim et al., 2013. PubMed ID: 24070693
  • Levy-Erez et al., 2010. PubMed ID: 20089052
  • Miura et al., 2000. PubMed ID: 11071380
  • Shatzky et al., 2000. PubMed ID: 10861667
  • Swanson 1963. PubMed ID: 13979626
  • Tüysüz et al., 2008. PubMed ID: 18322713

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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