ABSTRACT
INTRODUCTION: Recent literature highlights the clinical utility of genetic testing for patients with kidney disease. Genetic testing provides significant benefits for reproductive risk counseling, including the option of in vitro fertilization with preimplantation genetic testing for monogenic disease (PGT-M). PGT-M allows for a significant reduction in risk for a pregnancy affected with the familial disease. We aim to summarize our experience with PGT-M for genes with kidney involvement as either a primary or secondary feature of the disease. METHODS: All PGT-M tests performed by the reference laboratory between September 2010 and July 2020 were reviewed for clinical indication and cases for which the disease tested included a renal component. Each patient referred for PGT-M had an existing molecular genetic diagnosis themselves or in their family. Frequency of each condition, gene, inheritance pattern, and year over year increase in referral cases was analyzed. RESULTS: In the study cohort, the most common disease targeted was autosomal dominant polycystic kidney disease, caused by pathogenic variants in the PKD1 or PKD2 genes, which accounted for 16.5% (64/389) of cases. The 5 most common referral indications accounted for 51.9% (202/389) of the cases. Autosomal recessive inheritance accounted for 52.0% (26/50) of conditions for which PGT-M was performed. The number of PGT-M tests performed for conditions that included either primary or secondary kidney disease increased from 5 cases in 2010 to 47 cases in the 2020 study period. DISCUSSION/CONCLUSION: These data suggest that the pursuit of PGT-M by couples at risk for passing on conditions with a kidney component is common and has significantly increased since 2010. With this rising trend of patients undergoing PGT-M and the prerequisite of molecular genetic confirmation in the PGT-M process, this study underscores the importance of the reproductive component to a molecular genetic diagnosis for patients with kidney disease, especially as the accessibility of genetic testing and utilization by nephrologists grows.
Subject(s)
Genetic Testing , Kidney Diseases/diagnosis , Kidney Diseases/genetics , Adult , Humans , Laboratories, Clinical , Middle Aged , Preimplantation Diagnosis , Retrospective Studies , Young AdultABSTRACT
OBJECTIVES: HBB-related significant hemoglobinopathies have been anecdotally associated with low fetal fraction on noninvasive prenatal screening (NIPS). We sought to compare the difference in fetal fraction using NIPS in women with HBB-related significant hemoglobinopathies (HSH) and women with normal hemoglobin. STUDY DESIGN: This is a retrospective case-control study. Cases were women with a diagnosis of HSH using NIPS from a commercial laboratory. The comparison group was women with hemoglobin AA from a tertiary care center database. We tested for differences in median fetal fraction using quantile regression analysis, adjusting for maternal body weight and gestational age. RESULTS: This study includes 35 women with clinically significant HSH and a comparison group of 636 women with hemoglobin AA. Adjusting for gestational age and body weight, the median fetal fraction was 4.1 point lower in the HSH than in the comparison group (ß - 4.1; 95% -5.7 to -2.5, p < .05). The rate of no-calls due to low fetal fraction was significantly higher in the clinically significant HSH group than in the comparison group [HSH: n = 9/35, 25.7% versus comparison: n = 32/636, 5.0% (p < .001)]. CONCLUSION: Women with HSH were more likely to have a lower fetal fraction and ultimately a five-fold higher no-call rate. What's already known about this topic?Low fetal fraction is one of the most common causes of no-call result in noninvasive prenatal screeningHigh maternal weight, early gestational age and fetal aneuploidies are associated with low fetal fraction What does this study add?HBB-related significant hemoglobinopathies are associated with low fetal fractionReduction in fetal fraction due to HBB-related significant hemoglobinopathies may also result in higher no-call rate.