These authors contributed equally.
First HPSE2 missense mutation in urofacial syndrome
Version of Record online: 10 MAR 2011
© 2011 John Wiley & Sons A/S
Volume 81, Issue 1, pages 88–92, January 2012
How to Cite
Mahmood, S., Beetz, C., Tahir, M., Imran, M., Mumtaz, R., Bassmann, I., Jahic, A., Malik, M., Nürnberg, G., Hassan, S., Rana, S., Nürnberg, P. and Hübner, C. (2012), First HPSE2 missense mutation in urofacial syndrome. Clinical Genetics, 81: 88–92. doi: 10.1111/j.1399-0004.2011.01649.x
- Issue online: 12 DEC 2011
- Version of Record online: 10 MAR 2011
- Accepted manuscript online: 17 FEB 2011 08:29AM EST
- Received 19 November 2010, revised and accepted for publication 14 February 2011
- Ochoa syndrome;
- urofacial syndrome
Mahmood S, Beetz C, Tahir MM, Imran M, Mumtaz R, Bassmann I, Jahic A, Malik M, Nürnberg G, Hassan SAA, Rana S, Nürnberg P, Hübner CA. First HPSE2 missense mutation in urofacial syndrome.
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.