X-linked Intellectual Disability via the IL1RAPL1 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
9933 IL1RAPL1 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9933IL1RAPL181479 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.

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 ID cases in males.

Mental Retardation X-linked 21, MRX21 (also known as MRX34) is a form of ID, which can be both nonsyndromic and syndromic (Nawara et al. 2008. PubMed ID: 19012350; des Portes et al. 1998. PubMed ID: 9611075). The affected individuals present with variable features that may include (but may not be limited to) delayed psychomotor development, intellectual disability, hypotonia, seizures, strabismus, pectus excavatum, skin pigmentation abnormalities, hyperextensible joints, behavioral abnormalities including hyperactivity, impulsivity, oppositional disorder, depression, autism and mild facial dysmorphism such as elongated face, prominent jaw, synophrys, high nasal bridge, anteverted nostrils, high arched palate, and short philtrum (Kozák et al. 1993. PubMed ID: 8230164; Bhat et al. 2008. PubMed ID: 18005360; Franek et al. 2011. PubMed ID: 21484992). At least one affected female has been reported with autism and Asperger syndrome without any language delay (Kozák et al. 1993. PubMed ID: 8230164; Piton et al. 2008. PubMed ID: 18801879). Of note, carrier females can remain asymptomatic or develop mild intellectual disability and/or behavioral problems, suggesting incomplete penetrance in females (Kozák et al. 1993. PubMed ID: 8230164; Leprêtre et al. 2003. PubMed ID: 14610352, Tabolacci et al. 2006. PubMed ID: 16470793).

Genetics

Pathogenic variants (familial and de novo) in human ‘Interleukin-1 Receptor Accessory Protein-like 1’ (IL1RAPL1) have been reported in several cases with MRX21, a form of X-linked intellectual disability. IL1RAPL1 maps to chromosome Xp21.3-p21.2 and consists of 10 coding exons that translate into a 696 amino acid polypeptide of the transmembrane protein IL1RAPL1. IL1RAPL1 consists of three extracellular immunoglobulin-like domains, an intracellular Toll/IL1R-related (TIR) domain and a C-terminal domain that interacts with neuronal calcium sensor-1 (NCS-1) protein (Tabolacci et al. 2006. PubMed ID: 16470793). IL1RAPL1 plays a role in the down-regulation of voltage-dependent calcium channels (VGCC), calcium-dependent exocytosis and NGF-induced neurite outgrowth in PC-12 cells (Piton et al. 2008. PubMed ID: 18801879). Although small deletions, missense and nonsense variants have been reported in human IL1RAPL1 gene, the majority of the pathogenic variants are gross deletions/duplications and complex rearrangements involving IL1RAPL1 (Human Gene Mutation Database; Carrié et al. 1999. PubMed ID: 10471494). 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). Analytical sensitivity should be high because all pathogenic single nucleotide variants reported within this gene to date are detectable by sequencing.

To date, 29 gross deletions/duplications and complex rearrangements involving IL1RAPL1 have been reported (Human Gene Mutation Database). We expect the clinical sensitivity of this test to be <0.1% of ID cases.

Testing Strategy

This test provides full coverage of all coding exons of the IL1RAPL1 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

This test is primarily implicated for patients with intellectual disabilities who are negative for any kind of cytogenetic abnormalities, copy number variations, and Fragile-X syndrome, and also for family members of patients who have known IL1RAPL1 pathogenic variants. Prenatal diagnosis is possible, if the genetic diagnosis has been firmly established in an affected family member.

Gene

Official Gene Symbol OMIM ID
IL1RAPL1 300206
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mental Retardation, X-Linked 21 XL 300143

Citations

  • Bhat et al. 2008. PubMed ID: 18005360
  • Carrié et al. 1999. PubMed ID: 10471494
  • des Portes et al. 1998. PubMed ID: 9611075
  • Franek et al. 2011. PubMed ID: 21484992
  • Human Gene Mutation Database (Bio-base).
  • Kozák et al. 1993. PubMed ID: 8230164
  • Leprêtre et al. 2003. PubMed ID: 14610352
  • Nawara et al. 2008. PubMed ID: 19012350
  • Piton et al. 2008. PubMed ID: 18801879
  • Tabolacci et al. 2006. PubMed ID: 16470793
  • 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

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STAT and Prenatal Test Options are not available with Patient Plus.

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