Expanded carrier screening of recessive disorders (CarrierTest) in clinical practice

Česká verzia

Authors: J. Diblík; M. Bittóová; F. Lhota; F. Zembol; L. Dohnalová; Z. Vilímová; I. Soldátová; M. Hrabíková; I. Pavlechová; M. Koudová; D. Stejskal
Authors place of work: Centrum lékařské genetiky a reprodukční medicíny Gennet, s. r. o., Praha
Published in the journal: Čes-slov Pediat 2020; 75 (1): 5-10.
Category:

Summary

Objective: To evaluate the introduction of expanded carrier screening for disorders with autosomal recessive inheritance within the frame of preconception care particularly in couples with infertility or recurrent pregnancy loss.

Methods: CarrierTest is a custom designed test based on amplicon sequencing of target regions in 77 genes for detection of 835 pathogenic mutations causing more than 61 inherited disorders.

Results: We have examined 10752 individuals from the investigated couples during the period considered. In total we have detected 3899 pathogenic variants, most often in following genes: GJB2 (in 4.9% of individuals), CFTR (3.6%), SERPINA1 (2.6%), DHCR7 (2.6%), SMN1 (2.5%), PAH (2.3%), NBN (1.8%), CYP21A2 (3.3%), ATP7B (1.2%), PMM2 (1.1%), ACADVL (1.1%) and ACADM (1%). We have found a high risk of autosomal recessive disorder  in 67 couples (1.25%), most often both partners were carriers of mutations in GJB2 (18×), CFTR (13×), SMN1 (6×), CYP21A2 (6×), SERPINA1 (3×), PAH (3×), MEFV (3×), DHCR7 (2×), PMM2 (2×), ACADVL (2×), ACADM (2×), HEXA (2×) and ARSA (2×).

Conclusion: Results of CarrierTest provide the couples with information about the risk for their offspring. The severity of the risk differs depending on the gene and exact mutations. The findings thus must be assessed and communicated by a clinical geneticist so that couples can make informed decisions about further actions. The available preventive measures include preimplantation genetic testing, prenatal diagnosis as well as postnatal diagnosis (including prenatal screening) for early treatment.

Keywords:

Mutation – autosomal recessive inherited disorders – carrier status – preconception testing

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