Diagnostic Test Directory

Molecular Genetics Laboratory

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ARX-Related Disorders (ARX Sequencing)

  • Synonyms: X-linked lissencephaly with abnormal genitalia (XLAG), West syndrome, ISSX1, EIEE1, Partington Syndrome, X-linked Mental Retardation, X-linked Infantile Spasms
  • LIS Mnemonic: MBARXFSCR

    Collect

    Collect whole blood in a purple top (EDTA) tube (preferred). Extracted DNA is also acceptable.

    Volume Required

    3 ml whole blood or 2 ug extracted DNA

    Minimum Required

    3 ml whole blood

    Transport

    Refrigerate sample until shipment. Send the sample at room temperature with overnight delivery for receipt Monday through Friday within 24 hours of collection.

    Stability

    Whole blood can be refrigerated until shipment.

    Unacceptable conditions

    Heparinized specimens, severely hemolyzed specimens, frozen, clotted or possibly commingled specimens, blood in non-sterile or leaky containers, mislabeled or inappropriately labeled specimens.

    Specimen Handling

    Do not heat, freeze or centrifuge blood before shipment. Refrigerate sample until shipment.

Days Performed

Mon - Fri 9:00am to 4:00pm

Reported

4-6 weeks

CPT

81404

Disease Information

Clinical Features:

Mutations in the ARX gene lead to different nonsyndromic as well as syndromic forms of mental retardation: Partington syndrome (PRTS), X-linked infantile spasms syndrome (ISSX), X-linked lissencephaly with abnormal genitalia (XLAG), X-linked myoclonic epilepsy with spasticity and intellectual disability (XMESID), and non syndromic X-linked mental retardation (MRX). More recently, ARX mutations have been identified in several women with isolated agenesis of the corpus callosum (Proud syndrome) and in men with hydranencephaly.

Molecular Genetics:

ARX is located on Xp22 and contains 5 coding exons. ARX belongs to the Aristaless-related Paired-class homeodomain protein family and acts as a transcription factor involved in the organization of primary axes in a developing embryo. Mutations identified in ARX have included polyalanine repeat tract expansions, missense mutations, nonsense mutations, premature termination mutations, frameshift mutations, splice site mutations, duplications/insertions, and large deletions.

Test Methods:

PCR amplification and sequencing is performed on all coding exons of the ARX gene including splice junctions. The patient’s gene sequence is then compared to a reference sequence. Sequence variants are classified as mutations, variants of unknown significance or benign variants unrelated to disease. Variants of unknown significance may warrant further studies in the patient and other family members. Large deletions, mutations in promoters, deep intronic regions and other regulatory regions will not be identified with this assay.

Detection Rate:

Point mutations in the ARX gene are detected in 7-10% of cases with XLMR. The analytical sensitivity of this assay is ~99%.

Related Tests:

Rett syndrome: MECP2 Sequencing & Deletion/Duplication Analysis Atypical Rett syndrome: CDKL5 Gene Sequencing Known mutation analysis is available to family members for mutations previously identified by sequence analysis or deletion/duplication analysis. Prenatal Testing is available to adult females who are confirmed carriers of mutations. Please contact the laboratory director to discuss appropriate testing prior to collecting a prenatal specimen.

Results:

Test results with interpretation will be mailed and/or faxed to the referring physician or laboratory following completion of the test. Additional reports will be provided as requested.

Utility:

The clinical utility of such testing is to support a clinical diagnosis of the disease, facilitate genetic counseling, assess the risk to other first degree relatives and to facilitate testing of at - risk family members.

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