Loss-of-Function Mutations in HPSE2 Cause the Autosomal Recessive Urofacial Syndrome

• Published in: American journal of human genetics Vol. 86; no. 6; pp. 957 - 962
• Main Authors: Pang, Junfeng, Zhang, Shu, Yang, Ping, Hawkins-Lee, Bobbilynn, Zhong, Jixin, Zhang, Yushan, Ochoa, Bernardo, Agundez, Jose A.G., Voelckel, Marie-Antoinette, Gu, Weikuan, Xiong, Wen-Cheng, Mei, Lin, She, Jin-Xiong, Wang, Cong-Yi
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 11.06.2010; Cell Press; Elsevier
• Subjects: Biological and medical sciences; Chromosome Mapping; Chromosomes; Facies; Female; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genes; Genes, Recessive; Genetic disorders; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Glucuronidase - genetics; Humans; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Mutation; Pedigree; Proteins; Syndrome; Urologic Diseases - genetics; France; Colombia; United States > US; Human; Loss function; Autosomal character; Recessive character; Genetics; Mutation; Genetic disease
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2010.04.016

Previously, we localized the defective gene for the urofacial syndrome (UFS) to a region on chromosome 10q24 by homozygosity mapping. We now report evidence that Heparanse 2 ( HPSE2) is the culprit gene for the syndrome. Mutations with a loss of function in the Heparanase 2 ( HPSE2) gene were identified in all UFS patients originating from Colombia, the United States, and France. HPSE2 encodes a 592 aa protein that contains a domain showing sequence homology to the glycosyl hydrolase motif in the heparanase ( HPSE) gene, but its exact biological function has not yet been characterized. Complete loss of HPSE2 function in UFS patients suggests that HPSE2 may be important for the synergic action of muscles implicated in facial expression and urine voiding.