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Autosomal Recessive Congenital Ichthyosis (ARCI) via the ABCA12 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
9833 ABCA12 81479 81479,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9833ABCA1281479 81479,81479 $990 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 platform).

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

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

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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: ABCA12, TGM1, ALOXE3, ALOX12B, NIPAL4, CYP4F22 and PNPLA1. ABCA12 mutations cause recessive Harlequin ichthyosis (OMIM#242500) and autosomal recessive congenital ichthyosis type 4A (OMIM#601277). ABCA12 (ATP-binding cassette, sub-family A (ABC1), member 12) belongs to the superfamily of ATP-binding cassette (ABC) transporters which transport various lipids across extra- and intracellular membranes. ABCA12 mutations are mainly associated with Harlequin ichthyosis. To date, about 80 distinct causative mutations have been documented in HGMD (Human Gene Mutation Database). Mutations include missense (~30%), nonsense (30%), splicing mutations (12%), small deletions (~18%), small duplications (~4%). Four large deletions within ABCA12 and one case of paternal uniparental isodisomy have been documented. Homozygous and compound heterozygous truncating mutations lead to the Harlequin ichthyosis, while missense mutations are more associated with the severe type of lamellar ichthyosis (Lefévre et al., Hum Mol Genet 12(18):2369-2378, 2003; Castiglia et al. Clin Genet 76(4):392-397, 2009; Akiyama et al. Hum Mutat 31(10):1090-1096, 2010; Richard and Bale. GeneReviews, 2012). 

Clinical Sensitivity - Sequencing with CNV PGxome

ABCA12 is the major gene for Harlequin ichthyosis (Lefévre et al. Hum Mol Genet 12(18):2369-2378, 2003; Thomas et al. J Invest Dermatol 126(11):2408-2413, 2006). ABCA12 mutations account for ~5% of ARCI and 95% of Harlequin ichthyosis (Richard and Bale. GeneReviews, 2012).

Four large deletions within ABCA12 and one case of paternal uniparental isodisomy have been documented (Lefévre et al. Hum Mol Genet 12(18):2369-2378, 2003; Castiglia et al. Clin Genet 76(4):392-397, 2009).

Testing Strategy

This test provides full coverage of all coding exons of the ABCA12 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 Harlequin ichthyosis and the family members of patients who have known ABCA12 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in ABCA12.

Gene

Official Gene Symbol OMIM ID
ABCA12 607800
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Autosomal Recessive Congenital Ichthyosis (ARCI) via the CYP4F22 Gene
Autosomal Recessive Congenital Ichthyosis (ARCI) via the PNPLA1 Gene

Citations

  • Akiyama M. (2010). “ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.” Hum Mutat 31(10):1090-1096. PubMed ID: 20672373
  • Castiglia et al. (2009). “Trisomic rescue causing reduction to homozygosity for a novel ABCA12 mutation in harlequin ichthyosis.” Clin Genet 76(4):392-397.  PubMed ID: 19664001
  • Human Gene Mutation Database (Bio-base).
  • Lefévre et al. (2003). “Mutations in the transporter ABCA12 are associated with lamellar ichthyosis type 2.” Hum Mol Genet 12(18):2369-2378. PubMed ID: 12915478
  • 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
  • Thomas et al. (2006). “ABCA12 is the major harlequin ichthyosis gene.” J Invest Dermatol 126(11):2408-2413. PubMed ID: 16902423

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

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View Ordering Instructions

1) Select Test Method (Platform)


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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.
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