The importance of genetic counseling within planning of pregnancy by a patient with cystinuria and reproductive dysfunction

Kidney stone disease (KSD) is a common disease of the urinary system. It is important to determine the risk of transmitting the disease to the next generation for the patients suffering from the severe forms of urolithiasis. At the same time, an important aspect is to prepare a woman with KSD for the pregnancy. In the current article we describe a case of genetic counseling of a 37-year-old patient with cystinuria and infertility problem who came for consultation because of pregnancy planning. The woman and her husband underwent comprehensive laboratory and instrumental investigation together with molecular genetic analyses. Genetic diagnostics were carried out using the next generation sequencing method (NGS, from the English Next Generation Sequencing) with subsequent verification of the detected findings using the Sanger sequencing method. Before genetic counseling the couple had already undergone several genetic tests: karyotyping of both spouses (results 46,XX and 46,XY) and genetic testing of the woman for the presence of polymorphisms in the F2 and F5 genes, predisposing to the development of thrombophilia. As a result of genotyping, the patient was determined to have the rs1799963 polymorphism of the F2gene in a heterozygous state. During the consultation, to identify the genetic cause of cystinuria, the patient was prescribed whole exome sequencing. In the SLC7A9 gene, attributable for the development of cystinuria type B, a pathogenic variant c.313G>A (p.Gly105Arg) was identified in a homozygous form. The diagnosis of rare form of KSD was confirmed. In addition, the woman also had other findings associated with a number of hereditary diseases (genes ABCA4, GPR179, C2, GALC). Based on the results of exome sequencing of the patient’s husband, no matches were found for variants in the same genes of autosomal recessive diseases. Personalized recommendations were given for preparing and managing pregnancy, as well as preventing the development of complications of health condition in the future. Treatment of cystinuria was prescribed to the woman. The importance of medical genetic counseling is shown when planning childbearing in a patient with a rare form of KSD, who is additionally a heterozygous carrier of pathogenic variants in the genes of a number of monogenic diseases and genetically predisposed to thrombosis.

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