• Test code: 04721
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit

Invitae Alpha Thalassemia X-linked Intellectual Disability Test

Test description

This test analyzes the ATRX gene, which is associated with alpha thalassemia X-linked intellectual disability syndrome (ATRX). ATRX is characterized by distinctive facial features, severe developmental delays, genital anomalies, intellectual disability, and abnormal hemoglobin H production.

Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (1 gene)
  • alpha thalassemia X-linked intellectual disability syndrome (ATRX)

ATRX is a rare form of intellectual disability that is characterized by distinctive facial features including telecanthus, short nose, tented vermilion of the upper lip, and thick or everted vermilion of the lower lip with coarsening of the facial features over time. Genital anomalies including hypospadias and undescended testes, ambiguous genitalia, and normal external female genitalia in a 46,XY individual have also been reported. Skeletal findings include short stature, brachydactyly, tapering fingers, clinodactyly, digital contractures, overlapping digits, pes planus, varus and valgus foot deformations, pectus carinatum, kyphosis, scoliosis, and dimpling over the lower spine. Additionally profound developmental delay is a common feature. Although anemia manifestations characteristic of alpha-thalassemia may be observed, many individuals with ATRX syndrome have normal hematological findings and show no signs of thalassemia.

ATRX is the only known gene associated with alpha thalassemia X-linked intellectual disability syndrome.

ATRX is inherited in an X-linked pattern.

All males with a pathogenic variant in ATRX have been reported to be affected. Females with a pathogenic variant are typically asymptomatic carriers, though rare cases of females affected due to skewed X-inactivation have been reported.

There have been roughly 200 reported cases, but the exact prevalence remains unknown.

Testing for ATRX should be considered in individuals with a personal history of:

  • characteristic craniofacial features
  • microcephaly
  • genital anomalies
  • skeletal anomalies
  • laboratory findings of alpha-thalassemia
  • intellectual disability, typically in the severe to profound range

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ATRX NM_000489.4