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Abnormal retinal development associated with FRMD7 mutations

(2014) HUMAN MOLECULAR GENETICS. 23(15). p.4086-4089
Author
Organization
Abstract
Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder, often associated with FRMD7 mutations. As the appearance of the retina is reported to be normal based on conventional fundus photography, IIN is postulated to arise from abnormal cortical development. To determine whether the afferent visual system is involved in FRMD7 mutations, we performed in situ hybridization studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks post-conception). We show a dynamic retinal expression pattern of FRMD7 during development. We observe expression within the outer neuroblastic layer, then in the inner neuroblastic layer and at 9 weeks post-conception a bilaminar expression pattern. Expression was also noted within the developing optic stalk and optic disk. We identified a large cohort of IIN patients (n = 100), and performed sequence analysis which revealed 45 patients with FRMD7 mutations. Patients with FRMD7 mutations underwent detailed retinal imaging studies using ultrahigh-resolution optical coherence tomography. The tomograms were compared with a control cohort (n = 60). The foveal pit was significantly shallower in FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with significantly decreased optic disk area, retinal nerve fiber layer thickness, cup area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first time that abnormal afferent system development is associated with FRMD7 mutations and could be an important etiological factor in the development of nystagmus.
Keywords
ALBINISM, PAX6, MESSENGER-RNA, FOVEAL HYPOPLASIA, QUANTITATIVE-ANALYSIS, ACUITY, MODEL, CONGENITAL NYSTAGMUS, IDIOPATHIC INFANTILE NYSTAGMUS, OPTICAL COHERENCE TOMOGRAPHY

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Citation

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MLA
Thomas, Mervyn G, Moira Crosier, Susan Lindsay, et al. “Abnormal Retinal Development Associated with FRMD7 Mutations.” HUMAN MOLECULAR GENETICS 23.15 (2014): 4086–4089. Print.
APA
Thomas, M. G., Crosier, M., Lindsay, S., Kumar, A., Araki, M., Leroy, B., McLean, R. J., et al. (2014). Abnormal retinal development associated with FRMD7 mutations. HUMAN MOLECULAR GENETICS, 23(15), 4086–4089.
Chicago author-date
Thomas, Mervyn G, Moira Crosier, Susan Lindsay, Anil Kumar, Masasuke Araki, Bart Leroy, Rebecca J McLean, et al. 2014. “Abnormal Retinal Development Associated with FRMD7 Mutations.” Human Molecular Genetics 23 (15): 4086–4089.
Chicago author-date (all authors)
Thomas, Mervyn G, Moira Crosier, Susan Lindsay, Anil Kumar, Masasuke Araki, Bart Leroy, Rebecca J McLean, Viral Sheth, Gail Maconachie, Shery Thomas, Anthony T Moore, and Irene Gottlob. 2014. “Abnormal Retinal Development Associated with FRMD7 Mutations.” Human Molecular Genetics 23 (15): 4086–4089.
Vancouver
1.
Thomas MG, Crosier M, Lindsay S, Kumar A, Araki M, Leroy B, et al. Abnormal retinal development associated with FRMD7 mutations. HUMAN MOLECULAR GENETICS. 2014;23(15):4086–9.
IEEE
[1]
M. G. Thomas et al., “Abnormal retinal development associated with FRMD7 mutations,” HUMAN MOLECULAR GENETICS, vol. 23, no. 15, pp. 4086–4089, 2014.
@article{5696063,
  abstract     = {Idiopathic infantile nystagmus (IIN) is a genetically heterogeneous disorder, often associated with FRMD7 mutations. As the appearance of the retina is reported to be normal based on conventional fundus photography, IIN is postulated to arise from abnormal cortical development. To determine whether the afferent visual system is involved in FRMD7 mutations, we performed in situ hybridization studies in human embryonic and fetal stages (35 days post-ovulation to 9 weeks post-conception). We show a dynamic retinal expression pattern of FRMD7 during development. We observe expression within the outer neuroblastic layer, then in the inner neuroblastic layer and at 9 weeks post-conception a bilaminar expression pattern. Expression was also noted within the developing optic stalk and optic disk. We identified a large cohort of IIN patients (n = 100), and performed sequence analysis which revealed 45 patients with FRMD7 mutations. Patients with FRMD7 mutations underwent detailed retinal imaging studies using ultrahigh-resolution optical coherence tomography. The tomograms were compared with a control cohort (n = 60). The foveal pit was significantly shallower in FRMD7 patients (P < 0.0001). The optic nerve head morphology was abnormal with significantly decreased optic disk area, retinal nerve fiber layer thickness, cup area and cup depth in FRMD7 patients (P < 0.0001). This study shows for the first time that abnormal afferent system development is associated with FRMD7 mutations and could be an important etiological factor in the development of nystagmus.},
  author       = {Thomas, Mervyn G and Crosier, Moira and Lindsay, Susan and Kumar, Anil and Araki, Masasuke and Leroy, Bart and McLean, Rebecca J and Sheth, Viral and Maconachie, Gail and Thomas, Shery and Moore, Anthony T and Gottlob, Irene},
  issn         = {0964-6906},
  journal      = {HUMAN MOLECULAR GENETICS},
  keywords     = {ALBINISM,PAX6,MESSENGER-RNA,FOVEAL HYPOPLASIA,QUANTITATIVE-ANALYSIS,ACUITY,MODEL,CONGENITAL NYSTAGMUS,IDIOPATHIC INFANTILE NYSTAGMUS,OPTICAL COHERENCE TOMOGRAPHY},
  language     = {eng},
  number       = {15},
  pages        = {4086--4089},
  title        = {Abnormal retinal development associated with FRMD7 mutations},
  url          = {http://dx.doi.org/10.1093/hmg/ddu122},
  volume       = {23},
  year         = {2014},
}

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