Mutations in the NDP gene: contribution to Norrie disease, familial exudative vitreoretinopathy and retinopathy of prematurity.

Abstract

BACKGROUND:

To examine the contribution of mutations within the Norrie disease (NDP) gene to the clinically similar retinal diseases Norrie disease, X-linked familial exudative vitreoretinopathy (FEVR), Coat's disease and retinopathy of prematurity (ROP).

METHODS:

A dataset comprising 13 Norrie-FEVR, one Coat's disease, 31 ROP patients and 90 ex-premature babies of <32 weeks' gestation underwent an ophthalmologic examination and were screened for mutations within the NDP gene by direct DNA sequencing, denaturing high-performance liquid chromatography or gel electrophoresis. Controls were only screened using denaturing high-performance liquid chromatography and gel electrophoresis. Confirmation of mutations identified was obtained by DNA sequencing.

RESULTS:

Evidence for two novel mutations in the NDP gene was presented: Leu103Val in one FEVR patient and His43Arg in monozygotic twin Norrie disease patients. Furthermore, a previously described 14-bp deletion located in the 5' unstranslated region of the NDP gene was detected in three cases of regressed ROP. A second heterozygotic 14-bp deletion was detected in an unaffected ex-premature girl. Only two of the 13 Norrie-FEVR index cases had the full features of Norrie disease with deafness and mental retardation.

CONCLUSION:

Two novel mutations within the coding region of the NDP gene were found, one associated with a severe disease phenotypes of Norrie disease and the other with FEVR. A deletion within the non-coding region was associated with only mild-regressed ROP, despite the presence of low birthweight, prematurity and exposure to oxygen. In full-term children with retinal detachment only 15% appear to have the full features of Norrie disease and this is important for counselling parents on the possible long-term outcome.

• Authors: Joanne L Dickinson, Michèle M Sale, Abraham Passmore, Liesel M FitzGerald, Catherine M Wheatley, Kathryn P Burdon, Jamie E Craig, Supaporn Tengtrisorn, Susan M Carden, Hector Maclean, David A Mackey
• Journal: Clinical & experimental ophthalmology (Clin Exp Ophthalmol) 2006 Sep-Oct Vol. 34 Issue 7 Pg. 682-8 ISSN: 1442-6404 [Print] Australia
• PMID: 16970763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5' Untranslated Regions
• Eye Proteins
• NDP protein, human
• Nerve Tissue Proteins

Topics

• 5' Untranslated Regions (genetics)
• Adolescent
• Adult
• Child
• Chromatography, High Pressure Liquid
• Deafness (genetics)
• Eye Proteins (genetics)
• Female
• Gestational Age
• Humans
• Infant, Newborn
• Intellectual Disability (genetics)
• Male
• Middle Aged
• Mutation, Missense
• Nerve Tissue Proteins (genetics)
• Retinal Diseases (genetics)
• Retinopathy of Prematurity (genetics)
• Sequence Analysis, DNA
• Vitreoretinopathy, Proliferative (genetics)