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.



Disease Race/Ethnicity Detection
Rate, %
Prior Carrier
Risk
Residual Carrier Risk
After Negative Result
Alpha-Thalassemia Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian1 Up to 94 Varies by
ethnicity
Reduced
Beta-
Hemoglobinopathies
(Including Sickle
Cell Disease)
Mediterranean, Middle East, Southeast Asian, African, Chinese, Asian Indian1,2 99 Varies by
ethnicity
Reduced
Bloom Syndrome AJ3 99 1/134 1/13,301
Canavan Disease AJ3 >97 1/55 <1/1,801
  Non-AJ4,5 >50 N/A N/A
Cystic Fibrosis (CF) AJ6 >95 1/24 1/461
  Non-Hispanic Caucasian7 >90 1/25 1/241
  Hispanic American8 >88 1/46 1/376
  African American9 >78 1/65 1/292
  Asian American >53 1/94 1/199
Dihydrolipoamide
Dehydrogenase
Deficiency (DLD
Deficiency)
AJ3 >95 1/107 <1/2,121
Familial Dysautonomia AJ3 >99 1/31 <1/3,001
Familial Hyperinsulinism AJ3 90 1/68 1/671
Fanconi Anemia Type C AJ3 99 1/100 1/9,901
Fragile X Syndrome (FXS) Females10,11,12 99 1/259 1/25,801
Gaucher Disease AJ3 95 1/15 1/281
Glycogen Storage
Disease Type Ia
AJ3 >95 1/64 1/1,261
Caucasian13 >51 1/177 1/360
Joubert Syndrome 2 AJ14 99 1/107 1/10,601
Maple Syrup Urine
Disease
AJ3 95 1/97 1/1,921
Mucolipidosis Type IV AJ3 95 1/89 1/1,761
Nemaline Myopathy AJ3 >95 1/168 <1/3,341
Niemann-Pick
Disease Types A & B
AJ3 97 1/115 1/3,801
        2 SMN1
copy result
3 SMN1
copy result
Spinal Muscular
Atrophy (SMA)
Caucasian15 95 1/35 1/632 1/3,500
  AJ15 90 1/41 1/350 1/4,000
  Asian15 93 1/53 1/628 1/5,000
  African
American15
71 1/66 1/121 1/5,000
  Hispanic15 91 1/117 1/1,061 1/11,000
Tay-Sachs Disease AJ3 98 1/27 1/1,301  
  French-Canadian16 70 1/31 1/101  
  General Population16 46 1/300 1/555  
Usher Syndrome,
Type IF
AJ3 >75 1/147 <1/585  
Usher Syndrome,
Type IIIA
AJ3 >95 1/120 <1/2,381  
Walker-Warburg
Syndrome
AJ14 99 1/79 1/7,801  

 

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.

Please visit clinical education to view a recorded webinar about new guidelines and expanded carrier screening.