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Autosomal Recessive Congenital Ichthyosis (ARCI) via the TGM1 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
7843 TGM1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7843TGM181479 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

  • 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: TGM1, ALOXE3, ALOX12B, ABCA12, NIPAL4, CYP4F22 and PNPLA1. Transglutaminase-1, a catalytic membrane-bound enzyme encoded by TGM1 (OMIM# 190195) plays a key role in the formation of the cornified cell envelope in the epidermis of the skin. The enzyme catalyzes the ankylglutamine formation which leads to crosslinking of proteins and the conjugation of polyamines to proteins during skin formation. Cornified cells are the most insoluble component of the epidermis and function as the skin’s physical barrier. Mutations in TGM1 explain about 50% of ARCI and around 90% of lamellar ichthyrosis. To date, about 140 distinct causative mutations have been documented in HGMD (Human Gene Mutation Database). Mutations include missense (~60%), nonsense (15%), splicing mutations (7%) and small insertions/deletions (~11%). No large deletions/insertions involving TGM1 have been documented. The c.877-2A>G mutation was seen in about 30% of North American and Norwegian ARCI patients (Farasat et al. J Med Genet 46(2):103-111, 2009; Herman et al. Human Mutation 30(4): 537–547, 2009; and Richard and Bale. GeneReviews, 2012).

Clinical Sensitivity - Sequencing with CNV PG-Select

TGM1 mutations were identified in 115 out of 234 ARCI patients (Herman et al. Human Mutation 30(4): 537–547, 2009). Mutations in TGM1 explain ~90% of lamellar ichthyosis (Richard and Bale. GeneReview, 2012).

No gross deletions/duplications have been reported to date in TGM1 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the TGM1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with symptoms consistent with autosomal recessive congenital ichthyosis, particularly the lamellar type, and the family members of patients who have known TGM1 mutations. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in TGM1.

Gene

Official Gene Symbol OMIM ID
TGM1 190195
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Congenital Ichthyosis Of Skin AR 242300

Related Test

Name
Congenital Ichthyosis and Related Disorders Panel

Citations

  • Farasat  et al. (2009). “Novel transglutaminase-1 mutations and genotype-phenotype investigations of 104 patients with autosomal recessive congenital ichthyosis in the USA.” J Med Genet 46(2): 103-111. PubMed ID: 18948357
  • Herman et al. (2009). PubMed ID: 19241467
  • Human Gene Mutation Database (Bio-base).
  • 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

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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