A novel missense NDP mutation [p.(Cys93Arg)] with a manifesting carrier in an austrian family with Norrie disease

Audiol Neurootol. 2014;19(3):203-9. doi: 10.1159/000358866. Epub 2014 Apr 30.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blindness / congenital*
  • Blindness / genetics
  • Eye Proteins / genetics*
  • Family
  • Female
  • Genetic Diseases, X-Linked
  • Genetic Testing
  • Humans
  • Male
  • Mutation, Missense*
  • Nerve Tissue Proteins / genetics*
  • Nervous System Diseases / genetics*
  • Pedigree
  • Retinal Degeneration
  • Spasms, Infantile / genetics*

Substances

  • Eye Proteins
  • NDP protein, human
  • Nerve Tissue Proteins

Supplementary concepts

  • Norrie disease