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Female Carrier Screening

The Female Carrier Screening is a pan-ethnic screening panel that analyzes 30 genes for pathogenic mutations known to cause autosomal recessive and X-linked disorders seen at high carrier frequencies within the general population and within a few specific populations. The tested conditions vary in morbidity, mortality and treatment.

This is the most intensive carrier screening with the highest accuracy available.

  • Sequence variants and small insertions/deletions: unless otherwise specified, whole gene sequencing (coding regions and adjacent intronic/splice regions) is performed with >99% of bases covered by at least 20 independent sequence reads (“20x”). Additionally, intronic and promoter mutations specified in ClinVar and the Human Gene Mutation Database (HGMD) are targeted with >98% sensitivity.
  • Deletion/duplications (del/dup): copy number variants (also known as deletions/duplications, or del/dup for short) are detected using PMCDx’s sophisticated bioinformatic algorithm, CNVexonTM. Pathogenic variants found by this method are confirmed by Sanger sequencing, MLPA, or quantitative PCR (qPCR).
  • Fragile X: The trinucleotide repeat (CGG) expansion in the 5’ untranslated region of FMR1 is detected by repeat-primed PCR (rpPCR). Premutation carriers are sequenced by Sanger sequencing to detect AGG interruptions.
  • Spinal Muscular Atrophy: copy number changes in the SMN1 gene are screened by NGS and confirmed by MLPA. Point mutations for spinal muscular atrophy are not detected due to high sequence homology.
  • Pseudogenes: proprietary bioinformatics tools are employed to identify carrier mutations in disease genes (such as GBA for Gaucher disease and HBA1/HBA2 for alpha thalassemia) which have highly similar inactive counterparts.

Reporting options: Only variants classified as “Pathogenic” or “Likely Pathogenic” using the ACMG guidelines for sequence variant interpretation will be reported.

Detection rate: A broad range of laboratory and computational tools are employed to ensure the highest detection rate. The analytical detection rate for all genes is >98%.

*Male patients will not be screened for X-linked conditions (e.g., FMR1, etc.). If an X-linked condition is suspected in a male patient, please contact PMCDx or a genetics professional about diagnostic testing for that particular disorder.

Order Options

Sequencing (included)
Del/Dup (included)

 

Genes

ACADM, ASPA, ASS1, BLM, CFTR, CLN3, DHCR7, DMD, ELP1, FAH, FANCC, FMR1, G6PC, GAA, GALT, GBA, HBA1, HBA2, HBB, HEXA, IDUA, IVD, MMACHC, PAH, PEX1, PEX7, PKHD1, PMM2, SMN1, SMPD1 ( 30 genes )

Coverage:

99% at 20x

Specimen Requirements:

Blood (two 4ml EDTA tubes, lavender top) or Extracted DNA (3ug in EB buffer) or Buccal Swab or Saliva (kits available upon request)

Test Limitations:

All sequencing technologies have limitations. This analysis is performed by Next Generation Sequencing (NGS) and is designed to examine coding regions and splicing junctions. Although next generation sequencing technologies and our bioinformatics analysis significantly reduce the contribution of pseudogene sequences or other highly-homologous sequences, these may still occasionally interfere with the technical ability of the assay to identify pathogenic variant alleles in both sequencing and deletion/duplication analyses. Sanger sequencing is used to confirm variants with low quality scores and to meet coverage standards. If ordered, deletion/duplication analysis can identify alterations of genomic regions which include one whole gene (buccal swab specimens and whole blood specimens) and are two or more contiguous exons in size (whole blood specimens only); single exon deletions or duplications may occasionally be identified, but are not routinely detected by this test. Identified putative deletions or duplications are confirmed by an orthogonal method (qPCR or MLPA). This assay will not detect certain types of genomic alterations which may cause disease such as, but not limited to, translocations or inversions, repeat expansions (eg. trinucleotides or hexanucleotides), alterations in most regulatory regions (promoter regions) or deep intronic regions (greater than 20bp from an exon). This assay is not designed or validated for the detection of somatic mosaicism or somatic mutations.

Gene Specifics:

Gene Notes
SMN1 The current testing method detects sequencing variants in exon 7 and copy number variations in exons 7-8 of the SMN1 gene (NM_022874.2). Sequencing and deletion/duplication analysis are not performed on any other region in this gene. About 5%-8% of the population have two copies of SMN1 on a single chromosome and a deletion on the other chromosome, known as a [2+0] configuration (PubMed: 20301526). The current testing method cannot directly detect carriers with a [2+0] SMN1 configuration, but can detect linkage between the silent carrier allele and certain population-specific single nucleotide changes. As a result, a negative result for carrier testing greatly reduces but does not eliminate the chance that a person is a carrier. The 3-copy SMN1 state can be detected by this test and will be reported out if present.

CPT Codes:

CPT Code 81405, 81408, 81479

NOTE: The CPT codes listed on the website are in accordance with Current Procedural Terminology, a publication of the American Medical Association. CPT codes are provided here for the convenience of our clients. Clients who bill for services should make the final decision on which codes to use.

Resources

  1. Carrier screening for genetic conditions. Committee Opinion No. 691. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129:e41-55
  2. Carrier screening in the age of genomic medicine. Committee Opinion No. 690. American College of Obstetricians and Gynecologists. Obstet Gynecol 2017;129e35-40
  3. Edwards et al. Expanded Carrier Screening in Reproductive Medicine--Points to Consider. A Joint Statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol 2015; 125(3)
  4. Prior TW. Carrier screening for spinal muscular atrophy. ACMG Practice Guidelines. Genet Med 2008:10(11):840-842
  5. Sherman S et al. Fragile X syndrome: Diagnostic and carrier testing. ACMG Practice Guidelines. Genet Med 2005:7(8):584-587
  6. Watson MS et al. Cystic fibrosis population carrier screening: 2004 revision of American College of Medical Genetics mutation panel. ACMG Policy Statement. Genet Med 2004:6(5):387-391
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