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  • Test code: 04726
  • 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
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Invitae ARSE-Related Chondrodysplasia Punctata Test

Test description

The Invitae ARSE-Related Chondrodysplasia Punctata Test analyzes the ARSE gene, which is associated with a bone-and-cartilage-development disorder, X-linked chondrodysplasia punctata 1 (CDPX1). Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant can inform recurrence-risk assessment and genetic counseling.

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Primary panel (1 gene)
Add-on NSDHL-Related Disorders Gene (1 gene)

NSDHL-related disorders have clinical findings that overlap with chondrodysplasia punctata (CDP). In addition to CDP, individuals with CHILD syndrome have ichthyosis, limb defects, and visceral anomalies. Depending on the clinical presentation of the patient, clinicians may wish to broaden the analysis by including NSDHL. This gene can be added at no additional charge.

NSDHL

X-linked chondrodysplasia punctata (CDPX1) is characterized by stippled epiphyses that typically involve the ankle, toes, and fingers, although other bones may be affected. Males have shortened fingers and distinct facial features that include a flattening of the nasal bridge and nose. Calcifications of cartilage, particularly in the trachea, larynx, and bronchi, can cause breathing problems. Less commonly, features of developmental delay, hearing loss, vision abnormalities, or heart defects have been reported. Carrier females are not affected; however, some carrier females have been noted to have short stature.

Approximately 60%–75% of males with CDPX1 have a pathogenic sequence variant in ARSE. Contiguous Xp gene deletions that include ARSE may account for up to 25% of patients with CDPX1; however, the deletions can extend through to STS, XG, and MIC2X and present with additional features including ichthyosis, intellectual disability, anosmia, and hypogonadotropic hypogonadism.

Chondrodysplasia punctata 1 (CDPX1) is inherited in an X-linked dominant pattern.

CDPX1 is highly penetrant and exhibits clinical variability. While most male individuals have some features of varying severity, unaffected carrier males have also been described.

In one study, the prevalence of chondrodysplasia punctata was estimated at 1 in 500,000.

This test may be considered for male patients presenting with chondrodysplasia punctata, brachytelephalangy, and nasomaxillary hypoplasia.

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
ARSE NM_000047.2
NSDHL NM_015922.2