Nonphotosensitive Trichothiodystrophy 5 (X-linked Intellectual Disability) via the RNF113A 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
10477 RNF113A 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
10477RNF113A81479 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.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

For Reflex to PGxome pricing click here.

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

For Sanger Sequencing click here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Intellectual Disability (ID) is a heterogeneous group of neurodevelopmental disorders, characterized by congenital limitation in intellectual functioning (intelligence quotient, IQ ≤70), and adaptive behavior. It is diagnosed in ~1–3% of the population before 18 years of age (American Association of Intellectual and Developmental Disabilities, AAIDD). X-linked Intellectual Disability (XLID) contributes almost 10-15% of intellectual disability (ID) cases in males.

Deficiency of the RING finger protein 113A (RNF113A) leads to nonphotosensitive trichothiodystrophy type 5 (TTD5), a syndromic form of X-linked intellectual disability. TTD5 is primarily characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The clinical features may include (but may not be limited to) profound intellectual disability, developmental delay, speech problem, cerebellar atrophy, seizures, structural brain malformations such as hypoplastic corpus callosum and cerebellum, Dandy-Walker malformation, and also gait abnormalities, short stature, intrauterine growth restriction, progressive microcephaly, minimal body hair, recurrent infections, dysmorphic facies, aged appearance, and abnormalities of the head, neck, skin, hair, muscle and gastrointestinal, ophthalmological and genitourinary systems (Corbett et al. 2015. PubMed ID: 25612912).

Genetics

Pathogenic variants in RNF113A (also known as ZNF183) cause X-linked nonphotosensitive Trichothiodystrophy type 5, a syndromic form of intellectual disability. RNF113A consists of one coding exon and maps to chromosome Xq24, encoding a 343 amino acid polypeptide. RNF113A, an E3 ligase of ubiquitin-dependent pathway, contains a C3HC4-type RING finger domain and a Zinc-finger domain and is predicted to play a role in gene regulation and DNA repair (Frattini et al. 1997. PubMed ID: 9224902; Brickner et al. 2017. PubMed ID: 29144457). To date, one missense and one nonsense pathogenic variant have been reported (Tarpey et al. 2009. PubMed ID: 19377476; Corbett et al. 2015. PubMed ID: 25612912). The disease transmission pattern is primarily X-linked recessive.

Clinical Sensitivity - Sequencing with CNV PGxome

This test is predicted to detect pathogenic variants in <0.1% of individuals with intellectual disability (ID). In this context, it is important to note that although pathological variants over 800 genes have been identified in individuals with ID, a genetic diagnosis is still lacking in most cases due to extreme clinical and genetic heterogeneity of the condition (Vissers et al. 2016. PubMed ID: 26503795).

Testing Strategy

This test provides full coverage of all coding exons of the RNF113A 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.

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

Targeted Sanger sequencing in RNF113A is appropriate for the family members of patients with RNF113A pathogenic variants. Of note, a panel (or exome/genome) sequencing test would nearly always be more appropriate for patients with intellectual disabilities, unless previous clinical knowledge implicates the RNF113A gene. Prenatal testing is possible if the genetic diagnosis has been firmly established in an affected family member.

Gene

Official Gene Symbol OMIM ID
RNF113A 300951
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Trichothiodystrophy 5, nonphotosensitive XL 300953

Citations

  • Brickner et al. 2017. PubMed ID: 29144457
  • Corbett et al. 2015. PubMed ID: 25612912
  • Frattini et al. 1997. PubMed ID: 9224902
  • Tarpey et al. 2009. PubMed ID: 19377476
  • Vissers et al. 2016. PubMed ID: 26503795

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

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.

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