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  • Test code: 04424
  • 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 Holoprosencephaly Panel

Test description

The Invitae Holoprosencephaly Panel analyzes up to 10 genes that are associated with holoprosencephaly, a wide spectrum of brain malformations that are a result of incomplete development of the brain early in gestation. These genes were selected based on the available evidence to date to provide Invitae’s broadest test for holoprosencephaly.

Genetic testing of these genes 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 (6 genes)
Add-on Preliminary-evidence Genes for Holoprosencephaly (4 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

CDON FOXH1 NODAL PTCH1

  • holoprosencephaly (HPE)
    • alobar holoprosencephaly HPE
    • lobar HPE
    • middle interhemispheric variant (MIHV) type HPE
    • semilobar HPE
    • septopreoptic HPE

Holoprosencephaly (HPE) encompasses a spectrum of cerebral and facial malformations that occur when the forebrain fails to divide along the midline into distinct hemispheres during early embryonic development. HPE severity ranges from partial division of the forebrain to complete absence of the midline and accompanying clinical presentation, which is typically correlated with the degree of cerebral malformation and ranges from closely spaced eyes or a single central maxillary incisor to a single cyclopic eye and the presence of a proboscis (nose-like appendage). The majority of individuals with HPE have intellectual disability. Incomplete penetrance and widely variable expressivity, even within the same family, are observed.

The Invitae Holoprosencephaly Panel may identify a molecular cause of disease in more than 37-47% of cases with a positive family history, and 7% of cases with no family history.

Holoprosencephaly is inherited in an autosomal dominant pattern. De novo variants have been well-described in SHH (10%–30%), SIX3 (10%–20%), and ZIC2 (70%–80%).

Incomplete penetrance and widely variable expressivity, even within the same family, have been observed in cases of holoprosencephaly.

Holoprosencephaly occurs in approximately 1 in 10,000 live births.

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
CDON NM_016952.4
FGFR1 NM_023110.2
FOXH1 NM_003923.2
GLI2 NM_005270.4
NODAL NM_018055.4
PTCH1 NM_000264.3
SHH NM_000193.2
SIX3 NM_005413.3
TGIF1 NM_173208.2
ZIC2 NM_007129.3