Correlation of nonsense and frameshift mutations with severity of retinal abnormalities in neurofibromatosis 2.
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.
Feucht
Matthias
M
Departments of Ophthalmology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany..
Kluwe
Lan
L
Mautner
Victor-Felix
VF
Richard
Gisbert
G
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000704:Analysis of Variance; D002386:Cataract / Q000175:diagnosis / Q000235:genetics; D015984:Causality; D002648:Child; D018389:Codon, Nonsense; D015331:Cohort Studies; D015897:Comorbidity; D016001:Confidence Intervals; D005260:Female; D005451:Fluorescein Angiography; D016368:Frameshift Mutation; D016515:Genes, Neurofibromatosis 2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016518:Neurofibromatosis 2 / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011859:Radiography; D012164:Retinal Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D012720:Severity of Illness Index
D018389:Codon, Nonsense