Genotype-phenotype variations in five Spanish families with Norrie disease or X-linked FEVR

Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of...

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Bibliographic Details
Published in:Molecular vision 2005-09, Vol.11, p.705-712
Main Authors: Riveiro-Alvarez, Rosa, Trujillo-Tiebas, Maria José, Gimenez-Pardo, Ascension, Garcia-Hoyos, Maria, Cantalapiedra, Diego, Lorda-Sanchez, Isabel, Rodriguez de Alba, Marta, Ramos, Carmen, Ayuso, Carmen
Format: Article
Language:English
Subjects:
Adolescent
Blindness - congenital
Child, Preschool
Codon, Nonsense
Deafness - genetics
DNA Mutational Analysis
Exudates and Transudates
Eye Diseases - genetics
Eye Proteins - genetics
Female
Genetic Diseases, X-Linked - genetics
Genetic Variation
Genotype
Humans
Intellectual Disability - genetics
Male
Middle Aged
Nerve Tissue Proteins - genetics
Pedigree
Phenotype
Polymerase Chain Reaction
Retinal Dysplasia - genetics
Spain
Vitreous Body
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Summary:Norrie disease (OMIM 310600) is a rare X-linked disorder characterized by congenital blindness in males. Approximately 40 to 50% of the cases develop deafness and mental retardation. X-linked familial exudative vitreoretinopathy (XL-FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Both X-linked disorders are due to mutations in the NDP gene, which encodes a 133 amino acid protein called Norrin, but autosomal recessive (AR) and autosomal dominant (AD) forms of FEVR have also been described. In this study, we report the molecular findings and the related phenotype in five Spanish families affected with Norrie disease or XL-FEVR due to mutations of the NDP gene. The study was conducted in 45 subjects from five Spanish families. These families were clinically diagnosed with Norrie disease or similar conditions. The three exons of the NDP gene were analyzed by automatic DNA sequencing. Haplotype analyses were also performed. Two new nonsense mutations, apart from other mutations previously described in the NDP gene, were found in those patients affected with ND or X-linked FEVR. An important genotype-phenotype variation was found in relation to the different mutations of the NDP gene. In fact, the same mutation may be responsible for different phenotypes. We speculate that there might be other molecular factors that interact in the retina with Norrin, which contribute to the resultant phenotypes.
ISSN:1090-0535