Test name: Combination Testing - Next Generation Sequencing (NGS) / Microarray
- Autism/Intellectual Disability/Multiple Anomalies Next Generation Sequencing Panel AND High Density SNP Microarray can be ordered simultaneously as combination testing or in a tiered fashion to evaluate for common single gene causes of many overlapping indications.
NGS Test Information:
- Next generation sequencing (NGS), or “Next Gen” as it is frequently called, is a technology that analyzes multiple genes at once. It is a cost-effective method of testing many potentially causative genes simultaneously rather than ordering separate Sanger sequencing one gene at a time.
- Next Gen is most helpful in cases where a patient has findings suspicious of multiple potential genetic causes, generally the result of either clinical ambiguity due to marked phenotypic overlap between various syndromes or numerous genetic causes for a single disorder.
- Our systematic data analysis references the most current versions of primary genomic databases, which translates to better mutation classification (e.g., benign vs. pathogenic).
- Pathogenic changes are confirmed by traditional Sanger sequencing or by another appropriate testing method.
- Even after careful analysis, some variants cannot yet be classified as benign or pathogenic and, therefore, are variants of uncertain significance.
- Next Gen will identify sequence variation, but it will not identify large deletions or duplications. A complimentary test such as whole genome microarray analysis or gene-specific deletion/duplication analysis would be needed to identify genetic dosage abnormalities.
- Next Gen is NOT whole exome sequencing or whole genome sequencing. The test will only identify mutations in the genes included on the panel ordered.
Microarray Test Information:
- Postnatal High Density SNP array, or “microarray” as it is frequently called, is a technology that analyzes the genome for copy number changes, microdeletions, or microduplications, at a higher resolution than traditional karyotyping.
- Due to the increased diagnostic yield of microarray, the American College of Medical Genetics (ACMG) recommends microarray as a first tier test for individuals with intellectual disabilities, autism spectrum disorders, and/or multiple congenital anomalies.
- Microarray is more comprehensive and cost effective than ordering multiple FISH tests.
- The use of SNP (single nucleotide polymorphisms) technology allows us to evaluate for isodisomy (one form of uniparental disomy) (iUPD), segmental loss of heterozygosity (LOH), and regions of homozygosity (ROH), in addition to copy number changes.
- Our laboratory’s array platform uses a total of 2.6 million markers, 1.9 million non-polymorphic copy number probes, and 750,000 SNP probes, providing a global resolution of 5 Kb to 10 Kb for copy number changes and 5 Mb resolution for regions of homozygosity.
- Microarray testing will NOT detect single gene mutations, including small deletions or duplications, balanced chromosome arrangements such as translocations, or low level mosaicism.
*Reference Source: ARTICLE: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test
Specimen Requirements: Test kits are available – please contact the laboratory
- Blood: One 3-5 ml EDTA (purple top) tube
- For patients who have not previously been tested on NGS: Autism/ID/MA Panel GeneList1
- NGS: Autism/ID/MA Expanded Panel: 81302, 81321, and 81405(x3)
- For patients who have previously been tested on NGS: Autism/ID/MA Panel GeneList1
- NGS: Autism/ID/MA Expanded Panel:81405, 81407, and 81479
- High Density SNP Array: 81229 and 88230
Please contact the laboratory for questions regarding GeneList1 billing.
Pricing: Contact the laboratory billing staff for current costs
Required Forms: Postnatal Test Request Form
Turn-around time: Results are typically available in 6-10 weeks
- ARTICLE: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies. Am J Hum Gen 2010.
Step-by-step ordering instructions:
1) Access the postnatal test request form on the Human Genetics Laboratory website.
2) Complete the 2-page form. Under TEST SELECTION, mark the box next to the Combination Testing: NGS / Microarray to order tests simultaneously.
3) When ordering tiered testing, such as one test at a time, under SPECIAL TEST INSTRUCTIONS, indicate the order in which you would like the tests performed. For example, “Please complete microarray first. If negative, reflex to Next Gen Sequencing.”
4) Provide any clinical information that may be important for interpretation.
5) Obtain insurance pre-authorization when necessary; forms available.
6) Following HGL shipping & handling requirements, send completed test request form and specimen at room temperature within 24 hours of collection.