DNA icon

Intellectual Disability via the ACSL4 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
9897 ACSL4 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9897ACSL481479 81479,81479 $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.

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 backbone).

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

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

For Sanger Sequencing click here.

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

  • Renee Bend, PhD

Clinical Features and Genetics

Clinical Features

X-linked Intellectual Disability (XLID) contributes almost 10-15% of intellectual disability (ID) cases in males. Mental Retardation X-linked 63, MRX63 (alternately recognized as MRX68) is a condition of non-syndromic XLID that affects males and rarely carrier females (Raynaud et al. 2000). The skewed X-inactivation in favor of the normal X-chromosome among carrier females indicates the survival influence of the causal gene for MRX63 (Raynaud et al. 2000; Meloni et al. 2002). Affected males display mild to severe non-progressive intellectual disabilities (neurocognitive abnormalities) that is rarely associated with autistic features, but without seizures or facial dysmorphisms (Longo et al. 2003). Interestingly, carrier females have highly variable cognitive capacities, ranging from normal intelligence to moderate intellectual disabilities (Meloni et al. 2002).

Genetics

Pathogenic variants in ACYL-CoA Synthetase Long Chain Family Member 4, ACSL4 (also known as FACL4) have been reported in multiple families with MRX63. ACSL4 maps to chromosome Xq23. The brain-specific isoform of ACSL4 is the longest isoform that consists of 17 exons and encodes a 711 amino acid polypeptide. ACSL4 is highly expressed in adult human brain, especially in the cerebellar and hippocampal neurons, but not in the glial cells. Loss-of-function variants in ACSL4 abolish the catalytic activity of the enzyme, thus leading to MRX63 due to the deficiency of arachidonyl-CoA esters in the brain (Meloni et al. 2002). Nonsense, missense, splicing variants, and one multi-gene deletion including ACLS4 have been reported. 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 100 genes have been identified in individuals with X-linked intellectual disability (XLID), a genetic diagnosis is still lacking in most cases due to extreme clinical and genetic heterogeneity of the condition (Vissers et al. 2016). Analytical sensitivity should be high because the majority of pathogenic variants reported to date are detectable by sequencing.

To date, there is only one report of a major gross deletion that includes ACSL4 and 8 other genes. Based on this observation, we expect the clinical sensitivity of this test to be low.

Testing Strategy

This test provides full coverage of all coding exons of the ACSL4 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

This test is primarily implicated for patients with non-syndromic intellectual disabilities (X-linked) who are negative for any kind of cytogenetic abnormalities, copy number variations, Fragile-X syndrome and also for family members of the patients who have ACSL4 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
ACSL4 300157
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Mental Retardation, X-Linked 63 XL 300387

Citations

  • Longo I. et al. 2003. Journal of Medical Genetics. 40: 11-7. PubMed ID: 12525535
  • Meloni I. et al. 2002. Nature Genetics. 30: 436-40. PubMed ID: 11889465
  • Raynaud M. et al. 2000. European Journal of Human Genetics. 8: 253-8. PubMed ID: 10854107
  • Vissers L.E. et al. 2016. Nature Reviews Genetics. 17: 9-18. 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.
  • 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

loading Loading... ×

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: $
×
Copy Text to Clipboard
×