Classifying and evaluating fetuses with multicystic dysplastic kidney in etiologic studies

Area of Science:

• Medical Genetics
• Fetal Medicine
• Developmental Biology

Background:

• Multicystic dysplastic kidney (MCDK) is a frequent fetal malformation with an unclear etiology.
• Identifying the molecular causes of MCDK is crucial for prenatal diagnosis, genetic counseling, and prognosis.
• Current diagnostic methods have limitations in uncovering the full spectrum of genetic causes.

Purpose of the Study:

• To investigate the genetic etiology of multicystic dysplastic kidney (MCDK) using advanced molecular techniques.
• To evaluate the combined diagnostic yield of chromosome microarray analysis (CMA) and whole-exome sequencing (WES) in MCDK fetuses.
• To establish a foundation for improved prenatal consultation and prognostic assessment for MCDK cases.

Main Methods:

• Chromosome microarray analysis (CMA) was performed on 108 MCDK fetuses.
• Whole-exome sequencing (WES) was applied to 15 MCDK fetuses with normal karyotype and CMA results.
• Karyotype analysis was conducted as a preliminary genetic assessment.

Main Results:

• CMA identified 15 abnormal copy number variations (CNVs), including 14 pathogenic CNVs, in MCDK fetuses, significantly exceeding the detection rate of karyotype analysis (3.7%).
• Specific pathogenic CNVs identified include 17q12 microdeletion, 22q11.21 microdeletion, and others.
• WES detected Bardet-Biedl syndrome (BBS) 1 and BBS2 in two fetuses (13.3%) previously found to have normal karyotype and CMA, highlighting the complementary role of WES.

Conclusions:

• The combined application of CMA and WES substantially enhances the detection rate of genetic causes for MCDK.
• These advanced genetic techniques provide critical information for prenatal diagnosis, genetic counseling, and prognosis evaluation in MCDK.
• Further research into the genetic underpinnings of MCDK is warranted to improve clinical management.