Prenatal Diagnosis of Intragenic HNF1B Variant-Associated Renal Disease by Exome Sequencing

[摘要] Introduction: HNF1B-associated diseases are a group of genetic conditions that affect the kidney as well as other organ systems. Kidney anomalies are the most common symptoms. Other defects may include early-onset diabetes, genital abnormalities, and abnormalities of pancreas and liver function. Renal involvement has emerged as the earliest finding in HNF1B disease, even in prenatal life, with the most common feature being hyperechogenic kidneys. Case Presentation: In this study, we present 3 fetuses with bilateral renal hyperechogenicity identified by ultrasound in the second trimester. No pathogenic copy number variations were revealed by amniocentesis with chromosomal microarray analysis (CMA). Heterozygous variants in HNF1B were detected in all 3 fetuses by further investigation with exome sequencing (ES). Two pregnancies were terminated, and one was continued to term. Discussion and Conclusion: Because of the known high frequency of HNF1B aberrations in fetal hyperechogenic kidneys, HNF1B screening should be an integral part of prenatal diagnosis for such fetuses. ES should be recommended following or concurrently with CMA for rapid prenatal detection. The ES results would improve the diagnostic yield and are beneficial in guiding counseling and management.

[学科分类] 基础医学

[关键词] HNF1B gene;Prenatal diagnosis;Exome sequencing;Ultrasound;Hyperechogenic kidneys