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  1. Comprehensive Carrier Screening

Comprehensive Carrier Screening

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