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

TY - JOUR

T1 - Correlation of nonsense and frameshift mutations with severity of retinal abnormalities in neurofibromatosis 2.

AU - Feucht, Matthias

AU - Kluwe, Lan

AU - Mautner, Viktor Felix

AU - Richard, Gisbert

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 126

SP - 1376

EP - 1380

IS - 10

M1 - 10

ER -