Urinary tract effects of HPSE2 mutations.

Area of Science:

• Genetics and Molecular Biology
• Urology
• Developmental Biology

Background:

• Urofacial syndrome (UFS) is a rare autosomal recessive congenital disorder.
• It is characterized by facial grimacing and impaired bladder emptying.
• Mutations in the HPSE2 gene, encoding heparanase 2, are known causes of UFS, but the mutation spectrum is not fully understood.

Purpose of the Study:

• To investigate the spectrum of HPSE2 mutations in UFS patients.
• To explore the role of heparanase 2 in bladder function.
• To assess the prevalence of HPSE2 variants in other urinary disorders.

Main Methods:

• Genetic analysis of seven UFS kindreds to identify HPSE2 mutations.
• Functional studies using Hpse2 mutant mouse models.
• Analysis of HPSE2 variants in patients with non-neurogenic neurogenic bladder and nonsyndromic vesicoureteric reflux.
• Immunohistochemical analysis of pelvic ganglia.

Main Results:

• Seven UFS kindreds with distinct HPSE2 mutations were identified, including a novel deletion.
• Homozygous Hpse2 mutant mice exhibited bladder dysfunction mimicking human UFS.
• HPSE2 mutations were rare in other studied urinary conditions.
• Heparanase 1, heparanase 2, and LRIG2 were found in pelvic ganglia neural cell bodies.

Conclusions:

• Heparanase 2 is an autonomic neural protein crucial for bladder emptying.
• HPSE2 mutations are a significant cause of UFS.
• HPSE2 variants are uncommon in other urinary diseases with UFS-like symptoms.