Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene

Orsolya Orosz, Miklós Czeglédi, Irén Kántor, I. Balogh, Attila Vajas, Lili Takács, A. Berta, Gergely Losonczy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: NEUROD1 is a tissue-specific basic helix loop helix (bHLH) protein involved in the development and maintenance of the endocrine pancreas and neuronal elements. Loss of NEUROD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice. Heterozygous loss-of-function mutations in NEUROD1 have previously been described as a cause of maturity-onset diabetes of the young (MODY) and late-onset diabetes. To date, homozygous loss-of-function NEUROD1 mutations have only been detected in two patients. Both mutations caused permanent neonatal diabetes and severe neurologic defects, including visual impairment. However, a detailed ophthalmological phenotype of this novel syndrome has not yet been reported. Our aim was to characterize the ophthalmological phenotype associated with the previously reported homozygous c.427_428CT mutation in the NEUROD1 gene. Methods: The female patient was investigated on multiple occasions between 2009 (age 14) and 2014 (age 19), including visual acuity testing, automated perimetry, funduscopy, anterior-segment imaging, optical coherence tomography of the posterior pole, standard full-field electroretinography, and fundus-autofluorescence imaging. Results: The patient had nyctalopia, blurry vision, and visual field constriction from early childhood. Her best corrected visual acuity ranged between 20/25 and 15/25 during the investigation period. Perimetry showed concentric constriction of the visual field, sparing only the central 30 degrees in both eyes. The anterior segment did not show any morphological changes. Optical coherence tomography revealed total absence of the photoreceptor layer of the retina outside the fovea, where a discoid remnant of cone photoreceptors could be detected. Neither setting of the standard full-field electroretinography could detect any electrical response from the retina. Color fundus photos presented peripheral chorioretinal atrophy and central RPE mottling. A hyperreflective parafoveal ring was detected on fundus autofluorescent photos, a characteristic sign of hereditary retinal dystrophies. Conclusions: To the best of our knowledge, this is the first report on the ophthalmological phenotype associating with a homozygous NEUROD1 null mutation in humans. Our results indicate that the loss of NEUROD1 has similar functional and anatomic consequences in the human retina as those described in mice. The present description can help the diagnosis of future cases and provide clues on the rate of disease progression.

Original languageEnglish
Pages (from-to)124-130
Number of pages7
JournalMolecular Vision
Volume21
Publication statusPublished - Feb 5 2015

Fingerprint

Phenotype
Mutation
Retinal Dystrophies
Electroretinography
Retina
Visual Field Tests
Genes
Optical Coherence Tomography
Visual Fields
Constriction
Visual Acuity
Night Blindness
Retinal Cone Photoreceptor Cells
Optical Imaging
Vision Disorders
Deafness
Ataxia
Islets of Langerhans
Nervous System
Atrophy

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Orosz, O., Czeglédi, M., Kántor, I., Balogh, I., Vajas, A., Takács, L., ... Losonczy, G. (2015). Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene. Molecular Vision, 21, 124-130.

Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene. / Orosz, Orsolya; Czeglédi, Miklós; Kántor, Irén; Balogh, I.; Vajas, Attila; Takács, Lili; Berta, A.; Losonczy, Gergely.

In: Molecular Vision, Vol. 21, 05.02.2015, p. 124-130.

Research output: Contribution to journalArticle

Orosz, O, Czeglédi, M, Kántor, I, Balogh, I, Vajas, A, Takács, L, Berta, A & Losonczy, G 2015, 'Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene', Molecular Vision, vol. 21, pp. 124-130.
Orosz O, Czeglédi M, Kántor I, Balogh I, Vajas A, Takács L et al. Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene. Molecular Vision. 2015 Feb 5;21:124-130.
Orosz, Orsolya ; Czeglédi, Miklós ; Kántor, Irén ; Balogh, I. ; Vajas, Attila ; Takács, Lili ; Berta, A. ; Losonczy, Gergely. / Ophthalmological phenotype associated with homozygous null mutation in the NEUROD1 gene. In: Molecular Vision. 2015 ; Vol. 21. pp. 124-130.
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abstract = "Purpose: NEUROD1 is a tissue-specific basic helix loop helix (bHLH) protein involved in the development and maintenance of the endocrine pancreas and neuronal elements. Loss of NEUROD1 causes ataxia, cerebellar hypoplasia, sensorineural deafness, and severe retinal dystrophy in mice. Heterozygous loss-of-function mutations in NEUROD1 have previously been described as a cause of maturity-onset diabetes of the young (MODY) and late-onset diabetes. To date, homozygous loss-of-function NEUROD1 mutations have only been detected in two patients. Both mutations caused permanent neonatal diabetes and severe neurologic defects, including visual impairment. However, a detailed ophthalmological phenotype of this novel syndrome has not yet been reported. Our aim was to characterize the ophthalmological phenotype associated with the previously reported homozygous c.427_428CT mutation in the NEUROD1 gene. Methods: The female patient was investigated on multiple occasions between 2009 (age 14) and 2014 (age 19), including visual acuity testing, automated perimetry, funduscopy, anterior-segment imaging, optical coherence tomography of the posterior pole, standard full-field electroretinography, and fundus-autofluorescence imaging. Results: The patient had nyctalopia, blurry vision, and visual field constriction from early childhood. Her best corrected visual acuity ranged between 20/25 and 15/25 during the investigation period. Perimetry showed concentric constriction of the visual field, sparing only the central 30 degrees in both eyes. The anterior segment did not show any morphological changes. Optical coherence tomography revealed total absence of the photoreceptor layer of the retina outside the fovea, where a discoid remnant of cone photoreceptors could be detected. Neither setting of the standard full-field electroretinography could detect any electrical response from the retina. Color fundus photos presented peripheral chorioretinal atrophy and central RPE mottling. A hyperreflective parafoveal ring was detected on fundus autofluorescent photos, a characteristic sign of hereditary retinal dystrophies. Conclusions: To the best of our knowledge, this is the first report on the ophthalmological phenotype associating with a homozygous NEUROD1 null mutation in humans. Our results indicate that the loss of NEUROD1 has similar functional and anatomic consequences in the human retina as those described in mice. The present description can help the diagnosis of future cases and provide clues on the rate of disease progression.",
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