1. Comprehensive Carrier Screening

Comprehensive Carrier Screening

Krishna Kumar Kandaswamy, PhD 1 Maximilian E. R. Weiss 1 Gabriela-Elena Oprea, PhD 1 Prof. Arndt Rolfs, MD 1 Dr. Peter Bauer, MD 1 Florian Vogel 1 Katja Brüsehafer 1 Shivendra Kishore, PhD 1
June 21, 2018

These findings were presented at the annual European Human Genetics Conference (ESHG) 2018

Comprehensive Carrier Screening using a combination of NGS panel, ddPCR and RPA

Carrier screening is a genetic test used to determine if a healthy person is a carrier of a recessive genetic disease. The goal of carrier screening is to help individuals understand their risks of having a child with a genetic disorder and review the range of options available to guide pregnancy and family planning.In order to provide a comprehensive screening panel, a set of 331 genes relevant for autosomal and X-linked recessive disorders was selected. The CentoScreen® test includes a NGS panel targeting the 331 genes (assessing CCDS +/-20 bases and relevant deep intronic mutations from HGMD® and CENTOGENE’s proprietary variant database CentoMD®) and an in-house developed pipeline provides CNV calling on NGS data. Technically challenging but relevant risk genes (FMR1, SMN1, CYP21A2) are analyzed by additional assays based on ddPCR, RPA and Sanger.

  • An individual is a carrier of ~2.8 pathogenic variants on average2
  • Approximately 1 in 4 (24%) individuals are carriers for at least 1 disorder and 1 in 20 (5.2%) are carriers for multiple disorders3
  • The American College of Obstetricians and Gynecology recommends offering carrier screening to all pregnant women or couples considering pregnancy1
  • Early onset and high-severity disorders
  • Well-defined phenotype
  • High carrier frequency
  • Availability of treatment
  • Severe effect on quality of life

Case I: Family history and preconceptional testing

  • Previous undiagnosed deceased child
  • Child had no genetic testing
  • Suspected diagnosis of CDG1a
  • Couple worried about recurrence risk and other disorders

Available options for family planning:

  • Prenatal diagnosis in CVS or AF sample possible
  • Pre-implantation genetic diagnosis possible
  • Using a sperm or egg donor
  • Carrier testing for other family members at risk

Case II: No family history