Alpha-Thalassemia X-linked Intellectual Disability Syndrome via the ATRX 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
9835 ATRX 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9835ATRX81479 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 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

Alpha-Thalassemia X-linked Intellectual Disability (ATRX) syndrome is characterized by severe mental retardation, craniofacial abnormalities, genital abnormalities and alpha thalassemia due to mutation in the ATRX gene. Global development delays are common at infancy and in severe cases, cognitive function is profoundly impaired with patients being unable to walk independently or develop significant speech. Craniofacial abnormalities may include upswept frontal hair line, hypertelorism, epicanthic folds, hypotonic facies, and a small triangular upturned nose. Genital abnormalities range from hypospadia to ambiguous genitalia. About 85% of ATRX individuals have lowered Hemoglobin H levels but near normal red blood cell indicies. Mutations in the ATRX gene have been found in phenotypically similar X-linked intellectual disorders, including Carpenter-Waziri syndrome, Holmes-Gang syndrome, and Chudley-Lowre syndrome (Stevenson et al. 2010). Acquired mutations in ATRX have also been found in patients with alpha thalassemia myelodysplastic syndrome (ATMDS), a pre-leukemic condition typically found in elderly men (Steensma et al. 2004), and in low grade glioma (Kannan et al. 2012). Genetic testing is helpful in differential diagnosis of ATRX from other similar X-linked intellectual disorders including Coffin-Lowry Syndrome, MECP2 duplication syndrome and from classical alpha-thalassemia (Stevenson et al. 2010).

Genetics

ATRX is an X-linked recessive disorder with complete penetrance due to mutations in the ATRX gene. Female carriers have been reported to have ATRX syndrome in rare cases due to skewed X-chromosome inactivation (Stevenson et al. 2010). Mutations in the zinc finger domain (exons 7-9) and helicase domain (exons 17-20), with missense being most predominant, occur in more than 80% of individuals with ATRX (Gibbons et al. 2008; Picketts et al. 1996). However, mutations have been found throughout the coding region with nonsense, small insertions, small deletions, and splice site alterations being found in the minority of cases. A deep intronic variant denoted as c.6218-12574G>A has also been reported to cause ATRX syndrome through altered splicing (Picketts et al. 1996). Duplications in the ATRX gene have been reported to be causative for ATRX syndrome and represent <5% of cases (Thienpont et al. 2007). The ATRX protein is a member of the SWI/SNF chromatin remodeling protein family and functions to control telomere stability and chromatin cohesion (Mitson et al. 2011). The ATRX protein forms a complex with the histone chaperone DAXX to regulate gene expression of several genes including HBA1 and HBA2 leading the presence of alpha thalassemia in affected patients (Mitson et al. 2011).

Clinical Sensitivity - Sequencing with CNV PG-Select

Clinical sensitivity cannot be estimated because only a small number of patients have been reported (Stevenson et al. 2010). Analytical sensitivity for detection of known ATRX mutations is >95% (Stevenson et al. 2010. PubMed ID: 14592816).

Testing Strategy

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

Indications for Test

Patients with clinical features consistent with ATRX syndrome and hemoglobin electrophoresis indicating HbH are candidates for testing. In ~25% cases, female carriers for a pathogenic variant in the ATRX gene exhibit HbH inclusions following brilliant cresyl blue staining. Ideal candidates have a family history of ATRX syndrome. Genetic testing is often helpful in confirming diagnosis of ATRX (Stevenson et al. 2010).

Gene

Official Gene Symbol OMIM ID
ATRX 300032
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Gibbons RJ, Wada T, Fisher CA, Malik N, Mitson MJ, Steensma DP, Fryer A, Goudie DR, Krantz ID, Traeger-Synodinos J. 2008. Mutations in the chromatin-associated protein ATRX. Human Mutation 29: 796–802. PubMed ID: 18409179
  • Kannan K, Inagaki A, Silber J, Gorovets D, Zhang J, Kastenhuber ER, Heguy A, Petrini JH, Chan TA, Huse JT. 2012. Whole-exome sequencing identifies ATRX mutation as a key molecular determinant in lower-grade glioma. Oncotarget 3: 1194–1203. PubMed ID: 23104868
  • Mitson M, Kelley LA, Sternberg MJE, Higgs DR, Gibbons RJ. 2011. Functional significance of mutations in the Snf2 domain of ATRX. Human Molecular Genetics 20: 2603–2610. PubMed ID: 21505078
  • Picketts DJ, Higgs DR, Bachoo S, Blake DJ, Quarrell OW, Gibbons RJ. 1996. ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome. Human molecular genetics 5: 1899–1907. PubMed ID: 8968741
  • Steensma DP, Higgs DR, Fisher CA, Gibbons RJ. 2004. Acquired somatic ATRX mutations in myelodysplastic syndrome associated with thalassemia (ATMDS) convey a more severe hematologic phenotype than germline ATRX mutations. Blood 103: 2019–2026. PubMed ID: 14592816
  • Stevenson RE. 2010. Alpha-Thalassemia X-Linked Intellectual Disability Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301622
  • Thienpont B, Ravel T de, Esch H Van, Schoubroeck D Van, Moerman P, Vermeesch JR, Fryns J-P, Froyen G, Lacoste C, Badens C, others. 2007. Partial duplications of the ATRX gene cause the ATR-X syndrome. European Journal of Human Genetics 15: 1094–1097. PubMed ID: 17579672

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

loading Loading... ×

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.

Total Price: $
×
Copy Text to Clipboard
×