First HPSE2 missense mutation in urofacial syndrome

Clin Genet. 2012 Jan;81(1):88-92. doi: 10.1111/j.1399-0004.2011.01649.x. Epub 2011 Mar 10.

Abstract

Urofacial syndrome (UFS) describes the combination of urological problems and an inverted facial expression upon attempts to smile. Seventeen independent familial cases from different ethnicities have been described so far. Some of these have been linked to chromosome 10q. Very recently, homozygous loss-of-function mutations affecting the gene HPSE2 were identified in nine cases. Here, we describe a consanguineous UFS family from Pakistan with three of six siblings affected. We establish linkage to the chromosome 10q critical region and identify two non-synonymous HPSE2 variants. In silico analysis and screening of controls defines c.631T>C (p.Y211H) as a novel benign SNP and c.1628A>T (p.N543I) as the disease-causing mutation. Our study exemplifies the challenges in proper clinical diagnosis of UFS and, thereby, supports the hypothesis of the disease being under diagnosed. By identifying the first HPSE2 missense mutation it also provides a starting point for studies aimed at functionally understanding the unusual combination of symptoms as characterizing UFS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Amino Acid Sequence
  • Case-Control Studies
  • Child
  • Chromosomes, Human, Pair 10 / genetics*
  • DNA Mutational Analysis
  • Facies
  • Female
  • Genetic Linkage
  • Genetic Testing
  • Genotype
  • Glucuronidase / genetics*
  • Humans
  • Inheritance Patterns
  • Male
  • Molecular Sequence Data
  • Mutation, Missense*
  • Pedigree
  • Urologic Diseases / diagnosis
  • Urologic Diseases / genetics*

Substances

  • heparanase
  • Glucuronidase

Supplementary concepts

  • Urofacial syndrome