Congenital Ichthyosis and Related Disorders Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
4929 ABCA12 81479,81479 Order Options and Pricing
ABHD5 81479,81479
ALOX12B 81479,81479
ALOXE3 81479,81479
AP1S1 81479,81479
CERS3 81479,81479
CLDN1 81479,81479
CYP4F22 81479,81479
KRT1 81479,81479
KRT10 81479,81479
KRT2 81479,81479
KRT9 81479,81479
LIPN 81479,81479
NIPAL4 81479,81479
PNPLA1 81479,81479
POMP 81479,81479
SLC27A4 81479,81479
ST14 81479,81479
TGM1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
4929Genes x (19)81479 81479 $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

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

For Reflex to PGxome pricing click here.

Turnaround Time

18 days on average for standard orders or 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

Clinical Features and Genetics

Clinical Features

Congenital ichthyosis is a highly heterogeneous skin scaling disorder caused by abnormal skin keratinization. Autosomal recessive congenital ichthyosis (ARCI) includes harlequin ichthyosis, congenital ichthyrosis erythroderma and lamellar ichthyosis (Oji et al. 2010). The major clinical features are: congenital collodion membrane, ectropion, eclabium, alopecia, palmar-plantar hyperkeratosis, and hypohidrosis. Harlequin ichthyosis 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 are prominent erythroderma and white scales. Some patients have less severe congenital collodion membrane. Lamellar ichthyosis is characterized by brown dark, coarse scales with very mild erythema, alopecia and often includes congenital collodion membrane.

Genetics

Autosomal recessive ichthyosis are caused by pathogenic variants in the TGM1, ALOXE3, ALOX12B, ABCA12, CYP4F22, CLDN1, NIPAL4, PNPLA1, CERS3, LIPN, POMP, SLC27A4, and ST14 genes.

Pathogenic variants in the ABHD5 gene cause autosomal recessive Chanarin-Dorfman syndrome which is characterized by congenital ichthyosis, hepatosplenomegaly, vacuolated granulocytes and myopathy (Samuelov et al. 2011). Pathogenic variants in the AP1S1 gene are associated with MEDNIK, which is characterized by mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma (Montpetit et al. 2008).

Autosomal dominant ichthyosis and related conditions are caused by pathogenic variants in the KRT1, KRT2, KRT9 and KRT10 genes. KRT1 is involved in autosomal dominant Epidermolytic hyperkeratosis, KRT2 is involved in autosomal dominant Ichthyosis bullosa of Siemens, KRT9 is involved in autosomal dominant Palmoplantar keratoderma, epidermolytic, and KRT10 is involved in Ichthyosis, cyclic, with epidermolytic hyperkeratosis.

KRT1 and KRT10 are also involved in autosomal recessive Epidermolytic hyperkeratosis.

Clinical Sensitivity - Sequencing with CNV PGxome

~80% of Autosomal Recessive Congenital Ichthyosis (ARCI) patients have pathogenic variants in TGM1, ALOXE3, ALOX12B, ABCA12, NIPAL4, CYP4F22 and PNPLA1 (Fischer 2009; Richard and Bale 2014). In a recently study, 84% of the 113 patients with clinical diagnosed autosomal recessive ichthyosis were found to have bi-allelic pathogenic variants in one of these genes TGM1, ABCA12, ALOXE3, ALOX12B, NIPAL4, CYP4F22, PNPLA1, CERS3, SLC27A4 and ABHD5 (Pigg et al. 2016).

Pathogenic variants in TGM1 are responsible for 38~50% of ARCI cases; ALOX12B, ALOXE3, ABCA12 and CYP4F22 account for about 5 - 10% of ARCI cases each; and pathogenic variants in PNPLA1and NIPAL4 each account for only a small portion of ARCI cases. In addition, ABCA12 is the major gene for Harlequin ichthyosis and TGM1 is the major gene for Lamellar ichthyosis (Fischer 2009; Richard and Bale 2014).

KRT1 and KRT10 pathogenic variants were identified in 9 and 19 of 28 unrelated epidermolytic ichthyosis patients (Arin et al. 2011). KRT2 pathogenic variants were identified in 4 out of 26 families with keratinopathic ichthyoses (Hotz et al. 2016).

To date, only a few large deletions/duplications have been documented in the TGM1, ALOXE3, ABCA12, CYP4F22, ABHD5, KRT1, KRT10, and CERS3 genes (Pigg et al. 2016; Ullah et al. 2016; Lefèvre et al. 2006; Scott et al. 2013; Samuelov et al. 2011; Takeichi et al. 2016; Lamb et al. 2014; Radner et al. 2013; Human Gene Mutation Database). No large deletions/insertions in the ALOX12B, AP1S1, CLDN1, LIPN, NIPAL4, PNPLA1, POMP, SLC27A4, ST14, KRT2, and KRT9 genes have been reported.

Testing Strategy

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel provides 100% coverage of all coding exons of the genes 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 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

Individuals with symptoms consistent with congenital ichthyosis, Chanarin-Dorfman syndrome, MEDNIK, Epidermolytic hyperkeratosis, Palmoplantar keratoderma, Ichthyosis bullosa of Siemens.

Genes

Official Gene Symbol OMIM ID
ABCA12 607800
ABHD5 604780
ALOX12B 603741
ALOXE3 607206
AP1S1 603531
CERS3 615276
CLDN1 603718
CYP4F22 611495
KRT1 139350
KRT10 148080
KRT2 600194
KRT9 607606
LIPN 613924
NIPAL4 609383
PNPLA1 612121
POMP 613386
SLC27A4 604194
ST14 606797
TGM1 190195
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Arin M.J. et al. 2011. The British Journal of Dermatology. 164: 442-7. PubMed ID: 21271994
  • Fischer J. 2009. The Journal of Investigative Dermatology. 129: 1319-21. PubMed ID: 19434086
  • Hotz A. et al. 2016. Acta Dermato-venereologica. 96: 473-8. PubMed ID: 26581228
  • Human Gene Mutation Database (Bio-base).
  • Lamb R.C. et al. 2014. The British Journal of Dermatology. 171: 913-5. PubMed ID: 24720725
  • Lefèvre C. et al. 2006. Human Molecular Genetics. 15: 767-76. PubMed ID: 16436457
  • Montpetit A. et al. 2008. Plos Genetics. 4: e1000296. PubMed ID: 19057675
  • Oji V. et al. 2010. Journal of the American Academy of Dermatology. 63: 607-41. PubMed ID: 20643494
  • Pigg M.H. et al. 2016. Acta Dermato-venereologica. 96: 932-7. PubMed ID: 27025581
  • Radner F.P. et al. 2013. Plos Genetics. 9: e1003536. PubMed ID: 23754960
  • Richard G. and Bale S.J. 2014. Autosomal Recessive Congenital Ichthyosis. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301593
  • Samuelov L. et al. 2011. The British Journal of Dermatology. 164: 1390-2. PubMed ID: 21332462
  • Scott C.A. et al. 2013. The Journal of Investigative Dermatology. 133: 573-6. PubMed ID: 22992804
  • Takeichi T. et al. 2016. The Journal of Investigative Dermatology. 136: 2095-8. PubMed ID: 27349861
  • Ullah R. et al. 2016. International Journal of Dermatology. 55: 524-30. PubMed ID: 26578203

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

View Ordering Instructions

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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.

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