title: LRIG2 mutations cause urofacial syndrome.
abstract: Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.
authors: Centre for Genetic Medicine, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester and St. Mary's Hospital, Manchester Academic Health Science Centre, Manchester, UK.
authors: Helen M
authors: HM
authors: Stuart
authors: Neil A
authors: NA
authors: Roberts
authors: Berk
authors: B
authors: Burgu
authors: Sarah B
authors: SB
authors: Daly
authors: Jill E
authors: JE
authors: Urquhart
authors: Sanjeev
authors: S
authors: Bhaskar
authors: Jonathan E
authors: JE
authors: Dickerson
authors: Murat
authors: M
authors: Mermerkaya
authors: Mesrur Selcuk
authors: MS
authors: Silay
authors: Malcolm A
authors: MA
authors: Lewis
authors: M Beatriz Orive
authors: MB
authors: Olondriz
authors: Blanca
authors: B
authors: Gener
authors: Christian
authors: C
authors: Beetz
authors: Rita E
authors: RE
authors: Varga
authors: Omer
authors: O
authors: Gülpınar
authors: Evren
authors: E
authors: Süer
authors: Tarkan
authors: T
authors: Soygür
authors: Zeynep B
authors: ZB
authors: Ozçakar
authors: Fatoş
authors: F
authors: Yalçınkaya
authors: Aslı
authors: A
authors: Kavaz
authors: Burcu
authors: B
authors: Bulum
authors: Adnan
authors: A
authors: Gücük
authors: Wyatt W
authors: WW
authors: Yue
authors: Firat
authors: F
authors: Erdogan
authors: Andrew
authors: A
authors: Berry
authors: Neil A
authors: NA
authors: Hanley
authors: Edward A
authors: EA
authors: McKenzie
authors: Emma N
authors: EN
authors: Hilton
authors: Adrian S
authors: AS
authors: Woolf
authors: William G
authors: WG
authors: Newman
mesh_terms: D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D019066:Facies; D005190:Family; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D001743:Urinary Bladder / Q000473:pathology; D001750:Urinary Bladder, Neurogenic / Q000235:genetics; D014570:Urologic Diseases / Q000235:genetics* / Q000503:physiopathology
chemical_list: C488673:LRIG2 protein, human; D008562:Membrane Glycoproteins