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  • Test code: 04724
  • 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 Branchiootorenal Spectrum Disorders Panel

Test description

The Invitae Branchiootorenal Spectrum Disorders Panel analyzes two genes that are associated with branchiootorenal (BOR) syndrome and branchiootic syndrome (BOS). These genes were selected based on the available evidence to date to provide appropriate testing for the BOR and BOS phenotypic spectrum. Genetic testing can provide an accurate diagnosis, which may help guide medical management and surveillance decisions, predict disease progression and outcome, and indicate the recurrence risk.

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Primary panel (2 genes)
Add-on Townes-Brocks Syndrome Gene (1 gene)

Individuals with Townes-Brocks syndrome have highly variable phenotypic presentations and share ocular and renal system involvement with BOR and BOS. Given the significant overlap between the branchiootorenal spectrum disorders and Townes-Brocks syndrome, as well as the difficulty in differentiating between these disorders, analyzing the SALL1 gene, which is associated with Townes-Brocks syndrome, may be appropriate. The SALL1 gene can be included at no additional charge.

SALL1

Branchiootorenal spectrum disorders include branchiootic syndrome (BOS) and branchiootorenal (BOR) syndrome, which are characterized by hearing loss, structural defects of the ear, and branchial fistulas or cysts. Individuals with BOR syndrome also present with a range of renal abnormalities, such as renal hypoplasia, renal agenesis, renal dysplasia, renal cysts, vesicoureteral reflux, and hydronephrosis, which often lead to end-stage renal failure later in life.

Pathogenic variants in EYA1 account for 40% of branchiootorenal syndrome cases. Pathogenic variants in SIX1 account for 5% of branchiootorenal syndrome cases.

Branchiootorenal spectrum disorders are inherited in an autosomal dominant manner.

Penetrance for EYA1 and SIX1 is complete.

The prevalence of branchiootorenal spectrum disorders is estimated at 1 in 40,000 individuals.

This panel may be appropriate for confirmation of a clinical diagnosis or to establish a diagnosis in an individual with suspected branchiootorenal syndrome or branchiootic syndrome.

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
EYA1 NM_000503.5
SALL1 NM_002968.2
SIX1 NM_005982.3