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Histopathological and immunohistochemical findings associated with a null mutation in the Norrie disease gene
- Source :
- Ophthalmic Genetics. 18:71-77
- Publication Year :
- 1997
- Publisher :
- Informa UK Limited, 1997.
-
Abstract
- To determine the clinical, histopathological, and immunohistochemical ocular changes associated with a null mutation in the Norrie disease protein (NDP) gene.Tissue from a six-month-old boy with bilateral retrolental membranes and retinal detachment was obtained during vitreoretinal surgery. Histological sections were stained immunohistochemically with specific antibodies. No eye diseases with severe visual impairment or blindness were reported in the parents and their families. The NDP gene was analyzed by standard molecular genetic methods.A severe reduction in the number of retinal ganglion cells and a largely disarranged and hypoplastic inner nuclear layer were visible in the tissue specimen. Areas of the tissue with advanced pathology displayed massive fibrovascular proliferation in the vitreous cavity. Shrinkage and traction resulted in folding and detachment of the outer retina. Immunohistochemical reactivity for MIB(1) antigen demonstrated many proliferating cells in the vitreous, but no proliferative activity in the neuroretina. Retinal neurons showed a high grade of differentiation and expressed uniformly neuron-specific enolase and synaptophysin. A 1-base pair insertion (544/545insA) in the NDP gene was found in the affected boy. This mutation predicts a 'functional null-allele' due to a shift in the reading frame and, thus, a premature termination of mRNA translation after 55 instead of 133 amino acids.Loss of function of the NDP gene causes marked hypoplasia of the inner retinal cell layers and fibrovascular proliferation in the vitreous cavity, leading to retinal folding and detachment. The NDP therefore seems to play a critical role in terminal differentiation of the inner retinal cell layers and establishment and maintaining of anti-proliferative cellular interactions in the vitreous.
- Subjects :
- Male
Retinal Ganglion Cells
medicine.medical_specialty
Pathology
Antigens, Differentiation, Myelomonocytic
Nerve Tissue Proteins
Biology
Blindness
Retinal ganglion
03 medical and health sciences
0302 clinical medicine
Retinal Diseases
Antigens, CD
medicine
Humans
Eye Abnormalities
Eye Proteins
Genetics (clinical)
030304 developmental biology
Base Composition
0303 health sciences
Retina
Histocytochemistry
Retinal Detachment
Infant
Retinal detachment
medicine.disease
Immunohistochemistry
Null allele
eye diseases
Ophthalmology
medicine.anatomical_structure
Genes
Phosphopyruvate Hydratase
Mutation
Pediatrics, Perinatology and Child Health
Inner nuclear layer
030221 ophthalmology & optometry
Histopathology
sense organs
Norrie disease
Subjects
Details
- ISSN :
- 17445094 and 13816810
- Volume :
- 18
- Database :
- OpenAIRE
- Journal :
- Ophthalmic Genetics
- Accession number :
- edsair.doi.dedup.....05c1a75d55fe16bc48c56656e9eaa6fd