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Test Code D2313
Test Summary

Diagnostic whole genome sequencing and mitochondrial genome sequencing of the proband and 2 family members. Family samples are tested concurrently with the proband sample to further elucidate potential pathogenic changes. The StepOne® Comprehensive Biochemical Profile is a newborn screening test that detects more than 70 disorders in newborns. Both whole genome sequencing and StepOne analyses are performed from just a few drops of blood for the proband, and whole-genome sequencing is performed from saliva samples for the 2 family members. 

Turn-Around-Time (TAT)* 5  days
Acceptable Sample Types
Dried Blood Spots
Saliva
Acceptable Billing Types
Self (patient) Payment
Institutional Billing
*TAT starts after the sample and all required sample information is received at PerkinElmer Genomics, or after the benefits investigation is complete if requested for commercial insurance billing.

This test involves sequencing the whole genome with a mean coverage of 40X with a phenotype-driven variant analysis to minimize VUS. All variants identified will be analyzed according to American College of Medical Genetics and Genomics (ACMG) guidelines. This test includes the reliable detection of deletions, duplications, and other gene- and chromosomal-level events. Mitochondrial DNA analysis is included. A comprehensive biochemical profile called StepOne is also performed to identify the presence of more than 70 inherited disorders. This test screens for Recommended Universal Newborn Screening Panel (RUSP) disorders, which includes the full core and secondary panel recommended by ACMG along with other conditions that may not be found in state-mandated programs.

Seeking diagnosis in a timely fashion to change acute medical or surgical management and improve outcomes in acutely ill patients:

  • Newborns in intensive care units with suspected genetic diseases
  • Condition suggestive of a genetic disorder with a long differential diagnosis list
  • Genetically heterogeneous disease caused by likely pathogenic/pathogenic findings in multiple genes
  • Unclear or atypical presentation of a genetic disorder
  • Clinical suspicion of an inherited metabolic disorder.

Genetic disorders and congenital anomalies affect ~6% of live births and are the leading reason for hospitalization and mortality in infants. Whole-genome sequencing examines the cause of thousands of genetic diseases and precludes the need for their prior consideration in the differential diagnosis. By identifying an underlying genetic etiology of presentations at birth, the ultrarapid whole genome can significantly avoid the diagnosis dilemma and provide timely actionable information that permits precise interventions that may decrease morbidity and mortality. Family samples are tested concurrently with the proband sample to further elucidate potential pathogenic changes. The StepOne Comprehensive Biochemical Profile includes fatty acid oxidation disorders, organic acid disorders, amino acid disorders, and other conditions. Please refer to the Condition List sheet below for the complete list of conditions.

Whole-genome sequencing is performed on genomic DNA using 2X150bp reads on Illumina next-generation sequencing (NGS) systems at a mean coverage of 40X in the target region. The target region includes coding exons and 10bp of flanking intronic sequence of the known protein-coding RefSeq genes. This sequencing provides >97% coverage of the 22,000 genes in the genome at >40X. 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. 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 may be confirmed by Sanger sequence analysis before reporting at the director's discretion. This assay cannot detect variants in areas containing large numbers of tandem repeats. Mitochondrial DNA is sequenced and analyzed using the same pipeline. Copy number variation (CNV) analysis is designed to detect deletions and duplications of three exons or more; in some instances, due to the size of the exons or other factors, not all CNVs may be analyzed. Only CNVs related to phenotype are reported. 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). The StepOne Comprehensive Biochemical Profile is performed by tandem mass spectrometry as well as other technologies.

Dried Blood Spots
Collection Container(s):

Dried blood spot card

Collection:

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.
Condition: Follow the instructions provided with the collection set. Store the dried blood at ambient temperature for up to two days. If the specimen cannot be sent as soon as it is dry, the filter paper should be placed in a sealable plastic bag and stored in a refrigerator (≤ 8°C) or preferably in a freezer.
Shipping: Follow kit instructions. Double bag and ship overnight at ambient temperature.
Saliva
Collection Container(s):

Oragene™ Saliva Collection Kit or ORAcollect-Dx kit

Collection:

Collect saliva on an Oragene™ Saliva Collection Kit ORAcollect-Dx kit according to the manufacturer’s instructions. 

Condition: Store at ambient temperature. Do not refrigerate or freeze.
Shipping: Ship overnight at ambient temperature.
SPECIAL 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.

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