title: First HPSE2 missense mutation in urofacial syndrome.
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.
authors.affiliation: Department of Human Genetics & Molecular Biology, University of Health Sciences, Khayaban-e-Jamia Punjab, Lahore, Pakistan.
authors.forename: S
authors.initials: S
authors.lastname: Mahmood
authors.forename: C
authors.initials: C
authors.lastname: Beetz
authors.forename: M M
authors.initials: MM
authors.lastname: Tahir
authors.forename: M
authors.initials: M
authors.lastname: Imran
authors.forename: R
authors.initials: R
authors.lastname: Mumtaz
authors.forename: I
authors.initials: I
authors.lastname: Bassmann
authors.forename: A
authors.initials: A
authors.lastname: Jahic
authors.forename: M
authors.initials: M
authors.lastname: Malik
authors.forename: G
authors.initials: G
authors.lastname: Nürnberg
authors.forename: S A A
authors.initials: SA
authors.lastname: Hassan
authors.forename: S
authors.initials: S
authors.lastname: Rana
authors.forename: P
authors.initials: P
authors.lastname: Nürnberg
authors.forename: C A
authors.initials: CA
authors.lastname: Hübner
mesh_terms: D000293:Adolescent; D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002648:Child; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D004252:DNA Mutational Analysis; D019066:Facies; D005260:Female; D008040:Genetic Linkage; D005820:Genetic Testing; D005838:Genotype; D005966:Glucuronidase / Q000235:genetics*; D006801:Humans; D040582:Inheritance Patterns; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D014570:Urologic Diseases / Q000175:diagnosis / Q000235:genetics*; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase