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  • Test code: 05022
  • 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 TP63-Related Disorders Test

Test description

The Invitae TP63-Related Disorders Test analyzes the TP63 gene that is associated with a group of disorders characterized by varying combinations of ectodermal dysplasia, clefting, split-hand/foot malformations, lacrimal duct obstruction and hypopigmentation:

  • autosomal dominant acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome
  • ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (EEC3)
  • Hay-Wells syndrome (HWS)
  • limb-mammary syndrome
  • Rapp-Hodgkin syndrome
  • split-hand/foot malformation

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)
  • TP63-related disorders
    • acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome
    • ectrodactyly, ectodermal dysplasia, and and cleft lip/palate syndrome 3 (EEC3)
    • Hay-Wells syndrome (HWS)
    • limb-mammary syndrome
    • Rapp-Hodgkin syndrome
    • split-hand/foot malformation

TP63-related disorders represent a class of overlapping phenotypes that share a common spectrum of features including variable forms of ectodermal dysplasia, cleft lip/palate, hypopigmented skin, split-hand/foot malformation and/or syndactyly, and hypoplasia of the breasts and/or nipples. Features are typically present at birth, but the number and severity of symptoms may be genotype dependent.

Although TP63-related disorders are rare, nearly all individuals with a clinical diagnosis of a TP63-related disorder are found to have a pathogenic variant in TP63. The TP63 gene is estimated to account for approximately 10% of isolated split-hand/foot malformations.

TP63-related disorders are inherited in an autosomal dominant manner. Pathogenic variants can be inherited from an affected parent but in most cases (approximately 70%) the pathogenic variant occurs de novo.

This condition is considered highly penetrant; however, reduced penetrance has been reported in some families.

TP63-related disorders are rare and the prevalence is unknown.

This test could be considered for individuals with:

  • dermal erosions
  • ectodermal dysplasia (hypohidrosis, nail dysplasia, sparse hair)
  • hypopigmentation
  • lacrimal duct obstruction
  • split-hand/foot malformations
  • syndactyly
  • tooth abnormalities

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
TP63 NM_003722.4