QHerit^™ Expanded Carrier Screen specifications

Clinically supported, next-generation sequencing

The QHerit Expanded Carrier Screen is a DNA assay used to screen for selected single-gene mutations associated with an increased risk for specific diseases. These Mendelian mutations originate both from recessive single-gene disorders and X-linked single-gene disorders. QHerit includes tests recommended by American Congress of Obstetrics and Gynecology (ACOG), the American College of Medical Genetics and Genomics (ACMG), and Jewish advocacy groups to provide clear, clinically relevant results.

The QHerit Expanded Carrier Screen is a Laboratory Developed Test (LDT), which is subject to compliance with the Clinical Laboratory Improvement Amendments (CLIA) regulations and guidelines. This testing was developed and is performed in a Quest Diagnostics CLIA-certified, New York State-licensed, and College of American Pathologists (CAP)-accredited laboratory.

Comprehensive

• Reports on 22 inheritable diseases, as recommended for screening by ACOG, ACMG, and the JGDC
• Appropriate for patients of all ethnicities regardless of their ancestry or geographic origin
• Appropriate for women who are considering pregnancy, or are pregnant

Specimen type

• Whole blood

NOTE: The QHerit^™ Expanded Carrier Screen may not be ordered on fetal specimens. Fetal testing is available for each of the 22 individual diseases (i.e., not as a panel). Acceptable fetal specimens for each of the 22 individually orderable diseases are amniotic fluid or chorionic villus specimens.

How QHerit works

QHerit Expanded Carrier Screen is a validated, massively parallel sequencing platform panel of tests that determines carrier risk status for 22 guideline-recommended inheritable genetic diseases.

QHerit consists of a hotspot-based massively parallel sequencing platform (NGS) that uses a multiplex-polymerase chain reaction (PCR) amplification of specific gene regions followed by nucleotide sequence analysis to test for variants in 20 of the inheritable diseases. FXS variants are detected using PCR with detection by capillary electrophoresis. SMA variants are detected using real-time allele-specific PCR and a comparison between fluorescent signals of target and control PCR products to determine the copy number of the SMN1 gene and the CFTR control gene. Each of the 22 conditions in QHerit are separately orderable to enable partner testing when one member of a couple is identified as a carrier of a particular disease. Prenatal diagnosis (on amniotic fluid or chorionic villus specimens) is also available for each of the 22 individual diseases for at-risk couples.

AJ = Ashkenazi Jewish descent

References:
1. Origa R, Moi P. Alpha thalassemia. GeneReviews. https://www.ncbi.nlm.nih.gov/books/NBK1435/. Published November 1, 2005. Updated December 29, 2016. Accessed May 17, 2017.
2. Based on Quest Diagnostics samples tested 2004-2016.
3. Scott SA, Edelmann L, Liu L, et al. Experience with carrier screening and prenatal diagnosis for 16 Ashkenazi Jewish genetic diseases. Hum Mutat. 2010;31:1240-1250.
4. Sistermans EA, de Coo RF, van Beerendonk HM, et al. Mutation detection in the aspartoacylase gene in 17 patients with Canavan disease: four new mutations in the non-Jewish population. Eur J Hum Genet. 2000;8:557-560.
5. Kaul R, Gao GP, Matalon R, et al. Identification and expression of eight novel mutations among non-Jewish patients with Canavan disease. Am J Hum Genet. 1996;59:95-102.
6. Heim RA, Sugarman EA, Allitto BA. Improved detection of cystic fibrosis mutations in the heterogeneous U.S. population using an expanded, pan-ethnic mutation panel. Genet Med. 2001;3:168-176.
7. Sugarman EA, Rohlfs EM, Silverman LM, et al. CFTR mutation distribution among U.S. Hispanic and African American individuals: evaluation in cystic fibrosis patient and carrier screening populations. Genet Med. 2004;6:392-399.
8. Schrijver I, Ramalingam S, Sankaran R, et al. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics: novel mutations and assessment of a population-specific mutation spectrum. J Mol Diagn. 2005;7:289-299.
9. Friedman KJ, Leigh MW, Czarnecki P, et al. Cystic fibrosis transmembrane-conductance regulator mutations among African Americans. Am J Hum Genet. 1998;62:195-196.
10. Rousseau F, Rouillard P, Morel ML, et al. Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome. Am J Hum Genet. 1995;57:1006-1018.
11. Dombrowski C, Levesque S, Morel ML, et al. Premutation and intermediate-size FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Hum Mol Genet. 2002;11:371-378.
12. Monaghan KG, Lyon E, Spector EB, et al. ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. Genet Med. 2013;15:575-586.
13. Chou JY, Mansfield BC. Mutations in the glucose-6-phosphatase-alpha (G6PC) gene that cause type Ia glycogen storage disease. Hum Mutat. 2008;29:921-930.
14. Hoffman JD, Park JJ, Schreiber-Agus N, et al. The Ashkenazi Jewish carrier screening panel: evolution, status quo, and disparities. Prenat Diagn. 2014;34:1161-1167.
15. Hendrickson BC, Donohoe C, Akmaev VR, et al. Differences in SMN1 allele frequencies among ethnic groups within North America. J Med Genet. 2009;46:641-644.
16. Monaghan KG, Feldman GL, Palomaki GE, et al. Technical standards and guidelines for reproductive screening in the Ashkenazi Jewish population. Genet Med. 2008;10:57-72.

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