Urofacial Syndrome 1 via the HPSE2 Gene

Urofacial syndrome (UFS; Ochoa syndrome) is characterized by congenital urinary bladder dysfunction and abnormal facial expression while smiling, laughing and crying (Daly et al. 2010; Pang et al. 2010; Stuart et al. 2013). Typically appearing in early childhood or adolescence, urinary tract symptoms include lifelong urinary incontinence, recurrent urosepsis, vesicoureteral reflux and renal failure. Facial features may appear earlier than the urinary tract symptoms, but are usually unnoticed medically. Urofacial syndrome 1 and 2 are caused by recessive pathogenic variants in the HPSE2 and LRIG2 genes, respectively.

Urofacial syndrome 1 is an autosomal recessive disorder caused by defects in the HPSE2 gene (Daly et al. 2010; Pang et al. 2010). The HPSE2 gene has 12 coding exons that encode a heparanase enzyme, a protein implicated in biological processes involving remodeling of the extracellular matrix, including angiogenesis and tumor progression. Genetic defects of HPSE2 found to date include missense, nonsense and small deletion/insertions (Human Gene Mutation Database). An exon-level large deletion involving HPSE2 has also been reported.

Urofacial syndrome is known to be caused pathogenic variants in HPSE2 and LRIG2. Detection rate of pathogenic variants in the HPSE2 gene in a large cohort of patients with urofacial syndrome is unknown in the literature because only a limited number of cases have been reported. Based on the limited cases reported, pathogenic variants appear to be more common in HPSE2 as compared to LRIG2.

This test provides full coverage of all coding exons of the HPSE2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).