Rare copy number variants implicated in posterior urethral valves

Area of Science:

• Genetics
• Developmental Biology
• Urology

Background:

• The etiology of posterior urethral valves (PUV) remains largely unknown.
• Familial occurrence suggests a potential genetic component in PUV.
• Identifying genetic factors is crucial for understanding PUV pathogenesis.

Purpose of the Study:

• To identify novel copy number variants (CNVs) associated with isolated posterior urethral valves (PUV).
• To investigate the role of genetic factors in the development of PUV.

Main Methods:

• Analysis of 56 isolated PUV cases from New York State births (1998-2005).
• Genotyping using Illumina HumanOmni2.5 microarrays.
• Identification of autosomal and sex-linked CNVs using PennCNV and cnvPartition software, with stringent filtering criteria for candidate variants.

Main Results:

• Identified 47 rare, candidate PUV-associated CNVs in 32 cases.
• One case presented a 3.9 Mb deletion encompassing the BMP7 gene, known for its role in urethral development.
• Other notable CNVs included deletions, duplications, and triplications in genes such as PIK3R3, TSPAN1, FGF12, FAT1, TBX2, and TBX4.

Conclusions:

• Novel CNVs were identified in PUV cases, indicating a potentially larger role for genetic factors than previously recognized.
• Copy number variants may contribute to PUV in up to 57% of examined cases.
• Further investigation of genes within identified CNVs may elucidate genetic variants contributing to PUV.