Correlation of nonsense and frameshift mutations with severity of retinal abnormalities in neurofibromatosis 2.

Abstract

BACKGROUND:

Neurofibromatosis 2 (NF2) is an autosomal dominant disease that is characterized by nervous system tumors and ocular abnormalities.

OBJECTIVE:

To investigate genotype-phenotype correlations demonstrated for NF2-associated nervous system tumors, cataracts, and retinal lesions.

METHODS:

Forty-eight patients with NF2 from a tertiary neurological referral center underwent screening for constitutional NF2 mutations with multiple screening methods. Each patient underwent a complete ophthalmic examination, including fluorescein angiography to detect retinal vascular lesions.

RESULTS:

Retinal abnormalities (epiretinal membranes or retinal microaneurysms) were present in 25 of the 48 patients (52%). The occurrence of epiretinal membranes and retinal microaneurysms was highly correlated, but retinal abnormalities were not significantly correlated with cataracts (present in 39 of 47 patients [83%]). Logistic regression with full constitutional nonsense or frameshift mutations as the reference group demonstrated that somatic mosaicism was associated with a significantly lower likelihood of retinal abnormalities (odds ratio, 0.05; 95% confidence interval, 0.01-0.49).

CONCLUSIONS:

To our knowledge, this is the first genetic, clinical, and angiographic characterization of retinal abnormalities in NF2. Severe mutations are correlated with a more severe retinal involvement. Clinical Relevance Retinal abnormalities, which can be revealed by means of fluorescein angiography, are more common in patients with NF2 who have nonsense or frameshift mutations.

• Authors: Matthias Feucht, Lan Kluwe, Victor-Felix Mautner, Gisbert Richard
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 126 Issue 10 Pg. 1376-80 (Oct 2008) ISSN: 1538-3601 [Electronic] United States
• PMID: 18852415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Codon, Nonsense

Topics

• Adolescent
• Adult
• Age of Onset
• Analysis of Variance
• Cataract (diagnosis, genetics)
• Causality
• Child
• Codon, Nonsense
• Cohort Studies
• Comorbidity
• Confidence Intervals
• Female
• Fluorescein Angiography
• Frameshift Mutation
• Genes, Neurofibromatosis 2
• Genetic Predisposition to Disease
• Genetic Testing
• Genotype
• Humans
• Logistic Models
• Male
• Middle Aged
• Neurofibromatosis 2 (diagnostic imaging, epidemiology, genetics)
• Odds Ratio
• Phenotype
• Radiography
• Retinal Diseases (diagnostic imaging, epidemiology, genetics)
• Severity of Illness Index