The Risk of Hereditary Pathology During In Vitro Fertilization: A Clinical Case of the Birth of a Child with Cystic Fibrosis

Abstract

The risk of having a child with a monogenic disease cannot be excluded for any family. However, in a population of couples suffering from infertility, the frequency of heterozygous carriage of a monogenic pathology is higher than in a population with normal fertility. For example, a number of studies have proven the assotiation between male infertility and the carriage of pathogenic variants in the CFTR gene associated with cystic fibrosis. The purpose of the study was, based on a clinical case, to demonstrate the importance of testing for carriage of pathogenic genetic variants in the CFTR gene in married couples seeking assisted reproductive technologies (ART). For the analysis, medical documentation of the proband child and his parents were used. In a couple with confirmed male factor infertility, as a result of in vitro fertilization (IVF), a child was born who was diagnosed with cystic fibrosis at the age of 8 months (despite a negative result of neonatal screening). The child's father's sister also has cystic fibrosis, but the results of her genetic testing were not available. Preconception examination did not reveal common pathogenic variants in the CFTR gene in the father of the child; this study was not carried out on the mother of the child. The child’s diagnosis was confirmed by sequencing of the CFTR gene (2 pathogenic genetic variants were found in the compound heterozygous state: G194R and F508del). Subsequently, the mother was confirmed to be a carrier of the most common pathogenic variant of the CFTR gene — F508del, and the father, was a carrier of a rare variant G194R. Our observation illustrates the difficulty of diagnosing cases of cystic fibrosis and identifying carriers of this disease due to the large number of pathogenic variants of the CFTR gene. Professionals should be actively alert to the risk of having a sick child, especially in families with cases of the disease in relatives.

Acknowledgments
The authors express their gratitude to the Chief Physician of the Medical Center “Health Care of Mother and Child” — Elena B. Nikolaeva.

For citation
Kopylova EA, Deryabina SS, Kudryavtseva EV, Lagutina OV, Kovalev VV. The risk of hereditary pathology during in vitro fertilization: A clinical case of the birth of a child with cystic fibrosis. Bulletin of USMU. 2023;(4):27–39. (In Russ.). EDN: https://elibrary.ru/RZYTVZ.