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Autosomal Recessive Congenital Ichthyosis (ARCI) via the NIPAL4 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
8717 NIPAL4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8717NIPAL481479 81479,81479 $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.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

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

For Sanger Sequencing click here.

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

  • Stela Berisha, PhD, FACMG

Clinical Features and Genetics

Clinical Features

Autosomal recessive congenital ichthyosis (ARCI) is a highly heterogeneous skin scaling disorder caused by abnormal skin keratinization. ARCI includes harlequin ichthyosis, congenital ichthyrosis erythroderma and lamellar ichthyosis (Oji et al. J Am Acad Dermatol 63(4):607-641, 2010). The major clinical features are: congenital collodion membrane, ectropion, eclabium, alopecia, palmar-plantar hyperkeratosis, and hypohidrosis. Harlequin ichthyosis (OMIM#242500) is the severe form of ARCI. The infants are born covered with armor like thick scales separated with deep fissures. Patients may have bilateral ectropion and eclabium. Limb movement may be restricted by the thick scales which can lead to digital necrosis. Some patients may die at birth or shortly after birth due to sepsis, dehydration, and impaired thermoregulation. The main features of congenital ichthyosis erythroderma (OMIM#242100) are prominent erythroderma and white scales. Some patients have less severe congenital collodion membrane. Lamellar ichthyosis (OMIM#242300) is characterized by brown dark, coarse scales with very mild erythema, alopecia and often includes congenital collodion membrane.

Genetics

ARCI is caused by mutations in at least the following seven genes: NIPAL4, PNPLA1, ABCA12, TGM1, ALOXE3, ALOX12B, and CYP4F22. NIPAL4 mutations mainly cause autosomal recessive congenital ichthyosis type 6 (OMIM#612281), which is characterized by prominent erythroderma and white, superficial scales. The NIPAL4 protein coded by the NIPAL4 gene (OMIM#609383) is a component in the granular layer of the epidermis and functions as a magnesium transporter and may also serve as an endogenous lipid mediator for trioxilins A3 and B3 in the hepoxilin pathway. To date, only 10 causative mutations have been reported: 7 missense, 1 nonsense, and two splicing site mutations (Lefèvre et al. Hum Mol Genet 13(20):2473-2482. 2004; Richard and Bale. GeneReviews, 2012; Scott et al. J Invest Dermatol 133(2):573-576. 2013).

Clinical Sensitivity - Sequencing with CNV PGxome

NIPAL4 mutations account for only a small portion of ARCI cases overall (Richard and Bale. GeneReviews, 2012). Mutations in NIPAL4 were found in 16 of 18 (89%) families with the specific abnormal epidermal ultrastructures diagnosed by electron microscopy (Dahlqvist et al. J Med Genet 44(10):615-620, 2007).

No large deletions or duplications have been reported in NIPAL4 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the NIPAL4 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. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Candidates for this test are patients with symptoms consistent with autosomal recessive congenital ichthyosis, particularly patients with diffuse yellowish keratoderma on the palms and soles and the family members of patients who have known NIPAL4 mutations (Alavi et al. J Dermatol 39(4):375-381, 2012). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in NIPAL4.

Gene

Official Gene Symbol OMIM ID
NIPAL4 609383
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Autosomal Recessive Congenital Ichthyosis (ARCI) via the ALOX12B Gene
Autosomal Recessive Congenital Ichthyosis (ARCI) via the ALOXE3 Gene
Autosomal Recessive Congenital Ichthyosis (ARCI) via the CYP4F22 Gene
Autosomal Recessive Congenital Ichthyosis (ARCI) via the PNPLA1 Gene
Congenital Ichthyosis and Related Disorders Panel

Citations

  • Alavi et al. (2012). “Manifestation of diffuse yellowish keratoderma on the palms and soles in autosomal recessive congenital ichthyosis patients may be indicative of mutations in NIPAL4.J Dermatol 39(4):375-381. PubMed ID: 22098531
  • Dahlqvist et al. (2007). “Congenital ichthyosis: mutations in ichthyin are associated with specific structural abnormalities in the granular layer of epidermis.” J Med Genet 44(10):615-620. PubMed ID: 17557927
  • Human Gene Mutation Database (Bio-base).
  • Lefèvre et al. (2004). “Mutations in ichthyin a new gene on chromosome 5q33 in a new form of autosomal recessive congenital ichthyosis.” Hum Mol Genet 13(20):2473-2482. PubMed ID: 15317751
  • Oji et al. (2010). “Revised nomenclature and classification of inherited ichthyoses: results of the First Ichthyosis Consensus Conference in Sorèze 2009.” J Am Acad Dermatol 63(4):607-641. PubMed ID: 20643494
  • Richard G. and Bale SJ. (2012). “Autosomal Recessive Congenital Ichthyosis.” Genereview. PubMed ID: 20301593
  • Scott et al. (2013). “Targeted sequence capture and high-throughput sequencing in the molecular diagnosis of ichthyosis and other skin diseases.” J Invest Dermatol 133(2):573-576. PubMed ID: 22992804

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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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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