We are happy to accommodate requests for single genes or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered on our PGxome Custom Panel.

Sequencing cost to additional family members beyond trio: $790 (no report).

If report is needed for any additional family members, add $990.

The price to reflex to PGxome is $890. Sequencing cost for additional family members is $990 each (no report). If a PGxome report is needed for any family members, add $990 each.

Many known monogenic diseases may present early in life as severe neonatal or early childhood (<2 years old) illness. In the United States, such diseases account for ~20% of infant deaths and ~18% of pediatric hospitalizations (Kingsmore. 2012. PubMed ID: 22872815; Saunders et al. 2012. PubMed ID: 23035047). Recent studies have shown that genetic testing in such patients can be a very beneficial first-line test, as the results may provide a comprehensive molecular diagnosis that allows for early intervention for the patient, proper genetic counseling of the family, and may reduce the time spent in the diagnostic odyssey (Kingsmore. 2012. PubMed ID: 22872815; Saunders et al. 2012. PubMed ID: 23035047; Ceyhan-Birsoy et al. 2017. PubMed ID: 28079900).

In recent studies, thorough curation of clinically relevant genes has shown that ~500-1000 genes are typically associated with the majority of the severe infant or early childhood onset genetic disorders (Kingsmore. 2012. PubMed ID: 22872815; Ceyhan-Birsoy et al. 2017. PubMed ID: 28079900). Clinically, such patients may present with a wide-variety of non-specific symptoms, including but not limited to: respiratory distress, hypotonia, gastrointestinal distress, difficulty feeding, failure to thrive, lethargy, seizures, encephalopathy, cardiac defects, organomegaly, unusual facial features, abnormal odor, and metabolic disturbances (Saudubray and Cazorla. 2016). In addition, we have recently updated this test to include disorders that may present prenatally with abnormal ultrasound findings (Pangalos et al. 2016. PubMed ID: 27168972, genes analyzed from the most updated version of the Fetalis pipeline as of October 2018).

The majority of the genes in this test have been included in large gene panels designed for testing of disorders with severe neonatal or early childhood onset (Kingsmore. 2012. PubMed ID: 22872815; Ceyhan-Birsoy et al. 2017. PubMed ID: 28079900). In the more recent study by Ceyhan-Birsoy et al. (2017), genes were divided into several categories. For this test, we have included the majority of the genes classified as Category A (genes with definitive or strong evidence to cause a highly penetrant childhood-onset disorder) in their study. In addition, we have included a number of nuclear genes that have been recently associated with mitochondrial disorders (Craven et al. 2017. PubMed ID: 28415858) as well as recently reported genes associated with disorders with a prenatal, neonatal or early-childhood onset and phenotype relevant to this test (Pangalos et al. 2016. PubMed ID: 27168972)..

The full list of genes sequenced in this test is available under the “Summary and Pricing” tab.

The Neonatal Crisis Panel offers the traditional Patient Only testing as well as the options of Family testing (e.g., Duo, Trio, etc.) or Patient Plus testing. For Patient Plus, we require sending in both biological parents along with the patient’s specimen. However, Neonatal Crisis panel testing is performed only on the patient’s specimen, and depending on variants identified, parental specimens are then used for targeted testing to determine the phase of variants or to determine if a variant occurs de novo. For the highest diagnostic rate, Family - Trio testing is recommended.

For the Neonatal Crisis Panel, Next Generation Sequencing (NGS) technologies are used to cover the coding regions of targeted genes plus ~10 bases of non-coding DNA flanking each exon. Genomic DNA is extracted from patient specimens, as required. Patient DNA corresponding to the targeted genes is captured using Agilent Clinical Research Exome hybridization probes. Captured DNA is sequenced on the NovaSeq 6000 using 2x150 bp paired-end reads (Illumina, San Diego, CA, USA). The following quality control metrics are generally achieved: >97% of target bases are covered at >20x, and mean coverage of target bases >120x. Due to technical limitations, a subset of genes in this panel (~150) may have <97% coverage of the targeted bases within the gene; a list of these genes and associated coverage metrics is available if desired. Data analysis and interpretation is performed by the internally developed software Titanium-Exome. Variant calls are made by the GATK Haplotype caller and annotated using in house software and SnpEff. Variants are filtered and annotated using VarSeq (www.goldenhelix.com). Common benign and low quality variants are filtered from analysis.

For Sanger sequencing, polymerase chain reaction (PCR) is used to amplify targeted regions. After purification of the PCR products, cycle sequencing is carried out using the ABI Big Dye Terminator v.3.0 kit. PCR products are resolved by electrophoresis on an ABI 3730xl capillary sequencer. In nearly all cases, cycle sequencing is performed separately in both the forward and reverse directions.

Copy number variants (CNVs) are also detected from NGS data. We utilize a CNV calling algorithm that compares mean read depth and distribution for each target in the test sample against multiple matched controls. Neighboring target read depth and distribution and zygosity of any variants within each target region are used to reinforce CNV calls. All CNVs are confirmed using another technology such as aCGH, MLPA, or PCR before they are reported.

The report will not include all the observed variants in a patient due to the large number of genes included. However, the list of variants is available, along with our interpretations, upon request. Since this test is performed using exome capture probes, a reflex to exome sequencing may be ordered. Please see the PGxome page (Test #5000) for limitations and reporting criteria for this test.

This test is primarily implicated for patients with neonatal, infantile or early childhood onset severe disorders with a suspected genetic cause.