title: Norrie disease gene mutation in a large Costa Rican kindred with a novel phenotype including venous insufficiency.
abstract: A large Costa Rican kindred has been identified with 15 males affected with congenital blindness, progressive bearing loss, and venous insufficiency. Due to ophthalmological and audio-otological findings, including bilateral retinal dysplasia and detachment, progressive bilateral sensorineural hearing loss, and an X-linked pattern of inheritance, a tentative diagnosis of Norrie disease was considered. However, venous insufficiency is a clinical finding not reportedly associated with Norrie disease. Genetic linkage analysis using microsatellite repeat markers demonstrated linkage to Xp11.23-11.4 (z = 2.723 at theta = 0.0). A candidate gene approach using the Norrie disease gene (NDP), which maps to Xp11.3, revealed a point mutation in the third exon resulting in substitution of phenylalanine for leucine at position 61. The precise function of the gene product, norrin, has yet to be elucidated; however, it has been postulated to be involved in the regulation of neural cell differentiation and proliferation, although hypotheses have been considered for its role in vascular development in the eye. The finding of a mutation in NDP in association with peripheral vascular disease may provide valuable insight into the potential role of this gene in cellular processes.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Rehm
authors.forename: G A
authors.initials: GA
authors.lastname: Gutiérrez-Espeleta
authors.forename: R
authors.initials: R
authors.lastname: Garcia
authors.forename: G
authors.initials: G
authors.lastname: Jiménez
authors.forename: U
authors.initials: U
authors.lastname: Khetarpal
authors.forename: J M
authors.initials: JM
authors.lastname: Priest
authors.forename: K B
authors.initials: KB
authors.lastname: Sims
authors.forename: B J
authors.initials: BJ
authors.lastname: Keats
authors.forename: C C
authors.initials: CC
authors.lastname: Morton
mesh_terms: D001766:Blindness / Q000235:genetics*; D003364:Costa Rica; D003638:Deafness / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D016491:Peripheral Vascular Diseases / Q000235:genetics*; D010641:Phenotype; D014960:X Chromosome