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  • Test code: 04746
  • 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 KAT6B-Related Disorders Test

Test description

The KAT6B-Related Disorders Test analyzes the KAT6B gene that is associated with Say-Barber-Biesecker-Young-Simpson (SBBYSS) syndrome and genitopatellar syndrome (GPS). Both conditions are characterized by global developmental delay and intellectual disability, dysmorphic facies, hypotonia, cryptorchidism, congenital heart defects, patellar agenesis, structural brain defects, hearing loss, dental and palatal anomalies, and thyroid defects.

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)
  • Say-Barber-Biesecker-Young-Simpson (SBBYSS) syndrome
  • Genitopatellar syndrome

KAT6B-related disorders include Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and genitopatellar syndrome (GPS). Both present with global developmental delay and intellectual disability, dysmorphic facial features, hypotonia, cryptorchidism and congenital heart defects. Individuals with SBBYSS may also present with hearing loss, dental and palatal anomalies and thyroid abnormalities. GPS is generally considered more severe and also presents with patellar agenesis, structural brain defects, flexion contractures of the hips and knees, club feet and hydronephrosis and/or multiple renal cysts.

Approximately 55-75% of individuals with a clinical diagnosis of SBBYSS syndrome are found to have a pathogenic variant in KAT6B, while 83-100% of individuals with GPS are found to have a pathogenic variant in this gene.

KAT6B-related disorders are inherited in an autosomal dominant manner.

KAT6B-related disorders are thought to be highly penetrant. To date all causative variants reported have occurred de novo.

The prevalence of KAT6B-related disorders is not clearly established.

Diagnostic criteria have not been well-established for GPS. However, this test may be considered for individuals with two major features or one major feature and two minor features indicative of SBBYSS syndrome:

  • major features
    • blepharophimosis/ptosis
    • immobile mask-like face
    • lacrimal duct anomalies
    • long thumbs/great toes
    • patellar hypoplasia/agenesis
  • minor features
    • cleft palate
    • congenital heart defect
    • dental anomalies (hypoplastic teeth and/or delayed eruption of teeth)
    • genital anomalies (males: cryptorchidism)
    • global developmental delay/intellectual disability
    • hearing loss
    • hypotonia
    • thyroid anomalies

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
KAT6B NM_012330.3