title: A novel missense NDP mutation [p.(Cys93Arg)] with a manifesting carrier in an austrian family with Norrie disease.
abstract: Norrie disease is a rare, X-linked genetic syndrome characterized by combined congenital blindness and progressive hearing impairment. Norrie disease is caused by alterations in the NDP gene encoding the growth factor norrin that plays a key role in vascular development and stabilization of the eye, inner ear and brain. We identified a family with 3 affected deafblind males and a single female carrier presenting with a serous retinal detachment but normal hearing. Genetic analysis revealed a novel c.277T>C missense mutation causing the substitution of a hydrophobic cysteine to a hydrophilic arginine [p.(Cys93Arg)] within the highly conserved cysteine knot domain of the norrin protein. These results should expand the scope for amniocentesis and genetic testing for Norrie disease which is gaining in importance due to novel postnatal therapeutic concepts to alleviate the devastating retinal symptoms of Norrie disease.
authors.affiliation: Department of Otorhinolaryngology, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Parzefall
authors.forename: Trevor
authors.initials: T
authors.lastname: Lucas
authors.forename: Markus
authors.initials: M
authors.lastname: Ritter
authors.forename: Martin
authors.initials: M
authors.lastname: Ludwig
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ramsebner
authors.forename: Alexandra
authors.initials: A
authors.lastname: Frohne
authors.forename: Christian
authors.initials: C
authors.lastname: Schöfer
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
authors.forename: Klemens
authors.initials: K
authors.lastname: Frei
mesh_terms: D001766:Blindness / Q000151:congenital* / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D005190:Family; D005260:Female; D040181:Genetic Diseases, X-Linked; D005820:Genetic Testing; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009422:Nervous System Diseases / Q000235:genetics*; D010375:Pedigree; D012162:Retinal Degeneration; D013036:Spasms, Infantile / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C081848:NDP protein, human; D009419:Nerve Tissue Proteins