Structural eye disease

Gene: NF2

I don't know

Comment on list classification: Leaving this gene for red now, but flagging for review by the GMS as ocular manifestations other than cataracts are seen in some patients.

Created: 12 Jan 2021, 11:40 a.m. | Last Modified: 12 Jan 2021, 11:40 a.m.

Panel Version: 1.27

PMID: 33075808 - Sun et al 2020 - mouse model of Nf2 inactivation in embryonic eyes shows increased retinal pigmented epithelium proliferation which they propose cause defects resulting in persistent coloboma.

Additional papers supporting association of variants in NF2 and eye abnormalities

PMID: 31089872 - Waisberg et al 2019 - report on the eye examination of 8 unrelated NF2 patients from Brazil. 6 had germline variants (nonsense, frameshift, or splice site) in NF2. Ophthalmological features were present in all patients and varied from subtle retinal changes to a severe ocular phenotype preset at birth. Of those 6 with NF2 variants: cataracts 4/6, Hamartoma 4/6, Flame-shaped ERM 5/6, Strabismus 3/6, Retinal Tuft 2/6 and Choroidal nodules 3/6.

PMID: 29923868 - Painter et al 2019 - reviewed longitudinal ophthalmological data of 83 patients with NF2 who had a mutation present on blood testing, or identical mutations found in 2 or more tissue samples, or they met the updated Manchester modified criteria for a clinical diagnosis of NF2. Mutations in NF2 associated with severe systemic disease were found to result in greater visual morbidity at an earlier age.

PMID: 12210058 - Chan et al 2002 - looked at 40 ocular lesions from four NF2 patients, from three unrelated families. All had germline nonsense mutations in NF2. Cataracts were evident by pseudophakia in seven eyes, iris naevoid hyperplasia at the anterior surface in two eyes of two patients, and retinal lesions in all eyes.

PMID: 9246269 - Ragge et al 1997 - report 5 unrelated cases of patients with Neurofibromatosis 2 to illustrate the diverse ocular phenotypes seen in patients. Molecular analysis not given. The authors note that ocular manifestations are often the first sign of disease.

Created: 6 Jan 2021, 4:12 p.m. | Last Modified: 12 Jan 2021, 11:37 a.m.

Panel Version: 1.24

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Neurofibromatosis, type 2 OMIM:101000; neurofibromatosis type 2 MONDO:0007039

Publications

• 33075808
• 31089872
• 29923868
• 9246269
• 12210058

Red List (low evidence)

RH

Created: 19 Jun 2019, 3:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurofibromatosis, Type II; 101000

Red List (low evidence)

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed.

Created: 8 Mar 2022, 10:32 a.m. | Last Modified: 8 Mar 2022, 10:34 a.m.

Panel Version: 1.113

Submitted on behalf of Professor Nicola Ragge (Wessex and West Midlands GLH). RH

Created: 17 Apr 2019, 3:31 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neurofibromatosis, Type II; 101000

Variants in this GENE are reported as part of current diagnostic practice