This test analyzes 30 genes that have been associated with Joubert and Meckel-Gruber Syndromes
|Turn-Around-Time (TAT)*||2 - 3 weeks|
|Acceptable Sample Types||
Whole Blood (EDTA)
Dried Blood Spots
|Acceptable Billing Types||
Self (patient) Payment
|Self (patient) Price||$550.00|
|CPT Codes**||81443 (x1), 81479 (x1)|
This panel analyzes 30 genes that have been associated with Joubert and Meckel-Gruber Syndromes and disorders associated with Joubert and Meckel-Gruber Syndromes. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis detects most deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines.
This panel may be appropriate for individuals with a clinical suspicion of Joubert and Meckel-Gruber Syndromes and/or for individuals with a family history of Joubert and Meckel-Gruber Syndromes.
Joubert syndrome is a disorder that affects many parts of the body. The hallmark feature of Joubert syndrome is a combination of brain abnormalities known as the molar tooth sign. Other characteristics include low muscle tone, ataxia, fast or slow breathing, abnormal eye movements, delayed development, and intellectual disability. Joubert syndrome affects 1 in 80,000 and 1 in 100,000 newborns and can be caused by mutations in many genes (NIH, genetics home reference). Meckel-Gruber syndrome is a disorder with severe signs and symptoms. The most common features include enlarged kidneys with fluid-filled cysts, an occipital encephalocele, and the presence of extra fingers and toes. Because of their serious health problems, most individuals with Meckel-Gruber syndrome die before or shortly after birth. Meckel-Gruber syndrome affects 1 in 13,250 to 1 in 140,000 people worldwide and may be more common in certain populations. Meckel-Gruber syndrome can be caused by mutations in one of at least eight genes.
Sequencing is performed on genomic DNA using an Agilent targeted sequence capture method to enrich for the genes on this panel. Direct sequencing of the amplified captured regions was performed using 2X100bp reads on Illumina next-generation sequencing (NGS) systems. A base is considered to have sufficient coverage at 20X, and an exon is considered fully covered if all coding bases plus three nucleotides of flanking sequence on either side are covered at 20X or more. Low coverage regions, if any, are limited to ~1% or less of the nucleotides in the test unless a pathogenic variant explaining the phenotype is discovered. A list of these regions is available upon request. Alignment to the human reference genome (hg19) is performed, and annotated variants are identified in the targeted region. Variants are called at a minimum coverage of 8X and an alternate allele frequency of 20% or higher. Single nucleotide variants (SNVs) meeting internal quality assessment guidelines are confirmed by Sanger sequence analysis for records after results are reported. Indels and SNVs are confirmed by Sanger sequence analysis before reporting at the director's discretion. This assay cannot detect variants in regions of the exome that are not covered, such as deep intronic, promoter, and enhancer regions, areas containing large numbers of tandem repeats, and variants in mitochondrial DNA. Copy number variation (CNV) analysis detects deletions and duplications; in some instances, due to the size of the exons, sequencing complexity, or other factors, not all CNVs may be analyzed and/or may be difficult to detect. This assay is not designed to detect mosaicism; possible cases of mosaicism may be investigated at the discretion of the laboratory director. Primary data analysis is performed using Illumina DRAGEN Bio-IT Platform v.3.4.12. Secondary and tertiary data analysis is performed using PerkinElmer’s internal ODIN v.1.01 software for SNVs and Biodiscovery’s NxClinical v.6.1 or Illumina DRAGEN Bio-IT Platform v.3.4.12 for CNV and the absence of heterozygosity (AOH). Genes and/or exons located in pseudogene regions are not covered in this assay.
EDTA (purple top)
Infants (< 2-years): 2 to 3 mL; Children (>2-years): 3 to 5 mL; Older children and adults: Minimum 5mL. The blood tube should be inverted several times immediately after blood collection to prevent coagulation.
Clotted or hemolyzed samples are not accepted.
Required DNA Quantity by Test Type*:
- Next Generation Sequencing (NGS): Send >1000 ng total gDNA @ >15 ng/μL. Please ship samples in 10mM Tris. Do not use EDTA.
- Sanger Sequencing: Send >500 ng total gDNA @ >15 ng/μL (varies by the size of the gene and the variants requested).
- Non-Sanger Sequencing Tests: Send >500 ng total gDNA @ >15 ng/μL.
- Research Laboratories: DNA extracted in research laboratories is not acceptable. Only under exceptional circumstances (e.g., proband not available) will DNA extracted in a research laboratory be accepted for clinical testing. Additional testing (e.g., of other family members) may be required to confirm results.
- Laboratories outside the United States: Non-US laboratories are not subject to CLIA regulations and will be reviewed on a case-by-case basis. Please call to speak with a laboratory genetic counselor prior to submitting a DNA sample from any non-CLIA certified laboratory.
- Special Notes: If extracted DNA is submitted, information regarding the method used for extraction should be sent along with the sample.
Dried blood spot card
Follow kit instructions. Briefly, allow blood to saturate card until indicated areas are filled and blood has soaked through card. Air dry card at ambient temperature for at least 3 hours.
- NBS: Please contact PKIG to request the StepOne® kit.
- Gene Sequencing: Please contact PKIG to request the DBS collection kit.
- For pre-punched DBS: The required minimum 6 punches with 3.2 mm or 4 punches 4.75 mm.
Oragene™ Saliva Collection Kit or ORAcollect-Dx kit
Collect saliva on an Oragene™ Saliva Collection Kit ORAcollect-Dx kit according to the manufacturer’s instructions.
Please contact PerkinElmer to request the saliva collection kit for patients that cannot provide a blood sample as whole blood is the preferred sample.