The Experts below are selected from a list of 1632 Experts worldwide ranked by ideXlab platform
Nicola K. Ragge - One of the best experts on this subject based on the ideXlab platform.
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mutation analysis of the stra6 gene in isolated and non isolated Anophthalmia microphthalmia
Clinical Genetics, 2013Co-Authors: Nicolas Chassaing, Nicola K. Ragge, Ariana Kariminejad, A Buffet, J Martinovic, Siavash Ghaderisohi, P. CalvasAbstract:PDAC syndrome [Pulmonary hypoplasia/agenesis, Diaphragmatic hernia/eventration, Anophthalmia/microphthalmia (A/M) and Cardiac Defect] is a condition associated with recessive mutations in the STRA6 gene in some of these patients. Recently, cases with isolated Anophthalmia have been associated with STRA6 mutations. To determine the minimal findings associated with STRA6 mutations, we performed mutation analysis of the STRA6 gene in 28 cases with Anophthalmia. In 7 of the cases the Anophthalmia was isolated, in 14 cases it was associated with one of the major features included in PDAC and 7 had other abnormalities. Mutations were identified in two individuals: one with bilateral Anophthalmia and some features included in PDAC, who was a compound heterozygote for a missense mutation and a large intragenic deletion, and the second case with all the major features of PDAC and who had a homozygous splicing mutation. This study suggests that STRA6 mutations are more likely to be identified in individuals with A/M and other abnormalities included in the PDAC spectrum, rather than in isolated A/M cases.
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the fate of the oculomotor system in clinical bilateral Anophthalmia
Visual Neuroscience, 2012Co-Authors: Holly Bridge, Nicola K. Ragge, Ned Jenkinson, Alan Cowey, Kate E WatkinsAbstract:The interdependence of the development of the eye and oculomotor system during embryogenesis is currently unclear. The occurrence of clinical Anophthalmia, where the globe fails to develop, permits us to study the effects this has on the development of the complex neuromuscular system controlling eye movements. In this study, we use very high-resolution T2-weighted imaging in five anophthalmic subjects to visualize the extraocular muscles and the cranial nerves that innervate them. The subjects differed in the presence or absence of the optic nerve, the abducens nerve, and the extraocular muscles, reflecting differences in the underlying disruption to the eye's morphogenetic pathway. The oculomotor nerve was present in all anophthalmic subjects and only slightly reduced in size compared to measurements in sighted controls. As might be expected, the presence of rudimentary eye-like structures in the socket appeared to correlate with development and persistence of the extraocular muscles in some cases. Our study supports in part the concept of an initial independence of muscle development, with its maintenance subject to the presence of these eye-like structures.
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language networks in Anophthalmia maintained hierarchy of processing in visual cortex
Brain, 2012Co-Authors: Kate E Watkins, Nicola K. Ragge, Alan Cowey, Iona Alexander, Nicola Filippini, James Kennedy, Stephen M SmithAbstract:Imaging studies in blind subjects have consistently shown that sensory and cognitive tasks evoke activity in the occipital cortex, which is normally visual. The precise areas involved and degree of activation are dependent upon the cause and age of onset of blindness. Here, we investigated the cortical language network at rest and during an auditory covert naming task in five bilaterally anophthalmic subjects, who have never received visual input. When listening to auditory definitions and covertly retrieving words, these subjects activated lateral occipital cortex bilaterally in addition to the language areas activated in sighted controls. This activity was significantly greater than that present in a control condition of listening to reversed speech. The lateral occipital cortex was also recruited into a left-lateralized resting-state network that usually comprises anterior and posterior language areas. Levels of activation to the auditory naming and reversed speech conditions did not differ in the calcarine (striate) cortex. This primary ‘visual’ cortex was not recruited to the left-lateralized resting-state network and showed high interhemispheric correlation of activity at rest, as is typically seen in unimodal cortical areas. In contrast, the interhemispheric correlation of resting activity in extrastriate areas was reduced in Anophthalmia to the level of cortical areas that are heteromodal, such as the inferior frontal gyrus. Previous imaging studies in the congenitally blind show that primary visual cortex is activated in higher-order tasks, such as language and memory to a greater extent than during more basic sensory processing, resulting in a reversal of the normal hierarchy of functional organization across ‘visual’ areas. Our data do not support such a pattern of organization in Anophthalmia. Instead, the patterns of activity during task and the functional connectivity at rest are consistent with the known hierarchy of processing in these areas normally seen for vision. The differences in cortical organization between bilateral Anophthalmia and other forms of congenital blindness are considered to be due to the total absence of stimulation in ‘visual’ cortex by light or retinal activity in the former condition, and suggests development of subcortical auditory input to the geniculo-striate pathway.
Robyn V Jamieson - One of the best experts on this subject based on the ideXlab platform.
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isolated hypogonadotropic hypogonadism with sox2 mutation and Anophthalmia microphthalmia in offspring
European Journal of Human Genetics, 2011Co-Authors: Zornitza Stark, Rebecca Storen, Bruce Bennetts, Ravi Savarirayan, Robyn V JamiesonAbstract:Isolated hypogonadotropic hypogonadism (IHH) is a genetically heterogeneous condition in which patients frequently require assisted reproduction to achieve fertility. In patients with IHH who are otherwise well, no particular increased risk of congenital anomalies in the resultant offspring has been highlighted. Heterozygous mutations in SOX2 are the commonest single-gene cause of Anophthalmia/microphthalmia (A/M) and sometimes result in pituitary abnormalities. We report a family with a novel frameshift mutation in the SOX2 transactivation domain, p.Gly280AlafsX91, resulting in bilateral Anophthalmia and subtle endocrinological abnormalities in a male sibling, and unilateral microphthalmia in a female sibling. The mutation is present in their mother who has IHH, but has no eye disorders or other anomalies. She underwent assisted reproduction to achieve fertility. This report has important implications for the evaluation of patients with IHH, particularly in the setting of planned infertility treatment.
Holly Bridge - One of the best experts on this subject based on the ideXlab platform.
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Functional Brain Imaging During Extra-Ocular Light Stimulation in Anophthalmic and Sighted Participants: No Evidence for Extra-Ocular Photosensitive Receptors
'Frontiers Media SA', 2021Co-Authors: Holly Bridge, Gaelle S L Coullon, Rupal Morjaria, Stuart N. Peirson, Catherine E. Warnaby, Carina A. Pothecary, Brian Leatherbarrow, Russell G. Foster, Susan M. DownesAbstract:Light plays a critical role in regulating physiology and behavior, including both visual and non-visual responses. In mammals, loss of both eyes abolishes all of these responses, demonstrating that the photoreceptors involved are exclusively ocular. By contrast, many non-mammalian species possess extra-ocular photoreceptors located in the pineal complex and deep brain. Whilst there have been suggestions of extra-ocular photoreception in mammals, including man, evidence for these photoreceptors is limited. One approach to objectively determine the presence of such receptors is to measure brain responses to light using functional magnetic resonance imaging (fMRI). Moreover, by using participants who are clinically anophthalmic (congenital and acquired), it is possible to investigate potential light detection in the absence of the retina. Here we scanned participants with Anophthalmia and sighted participants in 4 different conditions; the first 3 conditions had a bright light source applied to the following locations: behind the right ear (“ear”), just below the nasal bridge and between the eyes (“head”), and at the right popliteal fossa (“knee”). In the fourth and final scan, the light source was switched off so that there was no light stimulus. All participants were scanned in a completely dark room. No consistent brain activity was detected during any of the light conditions in either sighted controls or anophthalmic participants. Thus, we do not provide any evidence for the presence of extraocular photoreceptors modulating human brain activity, despite recent evidence for gene transcription that may occur as a result of these photoreceptors
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structural and functional brain reorganisation due to blindness the special case of bilateral congenital Anophthalmia
Neuroscience & Biobehavioral Reviews, 2019Co-Authors: Holly BridgeAbstract:Abstract Investigating the changes in the brain that result from a loss of sensory input has provided significant insight into the considerable capacity of the brain to reorganise. One of the difficulties in studying sensory-deprived populations is that the time and extent of sensory loss vary significantly. In this review, we consider the changes in the human brain associated with complete absence of visual input resulting from bilateral congenital Anophthalmia, in which the eyes fail to develop. We describe the functional reorganisation and associated structural and connectivity changes that occur in the brain of those affected by the condition. By considering animal models of this condition, we investigate the changes that may be occurring on a scale that is not captured by human in vivo imaging techniques. Finally, we lay out a model pathway for taking auditory information to the occipital cortex that may be specific to Anophthalmia.
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early blindness shapes cortical representations of auditory frequency within auditory cortex
The Journal of Neuroscience, 2019Co-Authors: Elizabeth Huber, Holly Bridge, Kelly Chang, Ivan Alvarez, Aaron Hundle, Ione FineAbstract:Early loss of vision is classically linked to large-scale cross-modal plasticity within occipital cortex. Much less is known about the effects of early blindness on auditory cortex. Here, we examine the effects of early blindness on the cortical representation of auditory frequency within human primary and secondary auditory areas using functional magnetic resonance imaging (fMRI). We observe that 4 individuals with early blindness (2 females), including a subset of 5 individuals with Anophthalmia (1 female), a condition in which both eyes fail to develop, have lower response amplitudes and narrower voxel-wise tuning bandwidths compared to a group of typically sighted individuals. These results provide some of the first evidence in human participants for compensatory plasticity within non-deprived sensory areas as a result of sensory loss. SIGNIFICANCE STATEMENT Early blindness has been linked to enhanced perception of the auditory world, including auditory localization and pitch perception. Here we used functional magnetic resonance imaging to compare neural responses to auditory stimuli within auditory cortex across sighted, early blind, and anophthalmic individuals, in whom both eyes fail to develop. We find more refined frequency tuning in blind subjects, providing some of the first evidence in human subjects for compensation within non-deprived primary sensory areas as a result of blindness early in life.
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hierarchy of processing in ‘visual ’ cortex
2015Co-Authors: Kate E Watkins, Alan Cowey, Stephen M Smith, Iona Alex, James M. Kennedy, Nicola Ragge, Holly BridgeAbstract:Language networks in Anophthalmia: maintaine
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neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral Anophthalmia
Journal of Neurophysiology, 2015Co-Authors: Gaelle S L Coullon, Uzay E Emir, Kate E Watkins, Ione Fine, Holly BridgeAbstract:Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex, 1H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral Anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests th...
Kate E Watkins - One of the best experts on this subject based on the ideXlab platform.
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hierarchy of processing in ‘visual ’ cortex
2015Co-Authors: Kate E Watkins, Alan Cowey, Stephen M Smith, Iona Alex, James M. Kennedy, Nicola Ragge, Holly BridgeAbstract:Language networks in Anophthalmia: maintaine
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neurochemical changes in the pericalcarine cortex in congenital blindness attributable to bilateral Anophthalmia
Journal of Neurophysiology, 2015Co-Authors: Gaelle S L Coullon, Uzay E Emir, Kate E Watkins, Ione Fine, Holly BridgeAbstract:Congenital blindness leads to large-scale functional and structural reorganization in the occipital cortex, but relatively little is known about the neurochemical changes underlying this cross-modal plasticity. To investigate the effect of complete and early visual deafferentation on the concentration of metabolites in the pericalcarine cortex, 1H magnetic resonance spectroscopy was performed in 14 sighted subjects and 5 subjects with bilateral Anophthalmia, a condition in which both eyes fail to develop. In the pericalcarine cortex, where primary visual cortex is normally located, the proportion of gray matter was significantly greater, and levels of choline, glutamate, glutamine, myo-inositol, and total creatine were elevated in anophthalmic relative to sighted subjects. Anophthalmia had no effect on the structure or neurochemistry of a sensorimotor cortex control region. More gray matter, combined with high levels of choline and myo-inositol, resembles the profile of the cortex at birth and suggests th...
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the fate of the oculomotor system in clinical bilateral Anophthalmia
Visual Neuroscience, 2012Co-Authors: Holly Bridge, Nicola K. Ragge, Ned Jenkinson, Alan Cowey, Kate E WatkinsAbstract:The interdependence of the development of the eye and oculomotor system during embryogenesis is currently unclear. The occurrence of clinical Anophthalmia, where the globe fails to develop, permits us to study the effects this has on the development of the complex neuromuscular system controlling eye movements. In this study, we use very high-resolution T2-weighted imaging in five anophthalmic subjects to visualize the extraocular muscles and the cranial nerves that innervate them. The subjects differed in the presence or absence of the optic nerve, the abducens nerve, and the extraocular muscles, reflecting differences in the underlying disruption to the eye's morphogenetic pathway. The oculomotor nerve was present in all anophthalmic subjects and only slightly reduced in size compared to measurements in sighted controls. As might be expected, the presence of rudimentary eye-like structures in the socket appeared to correlate with development and persistence of the extraocular muscles in some cases. Our study supports in part the concept of an initial independence of muscle development, with its maintenance subject to the presence of these eye-like structures.
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language networks in Anophthalmia maintained hierarchy of processing in visual cortex
Brain, 2012Co-Authors: Kate E Watkins, Nicola K. Ragge, Alan Cowey, Iona Alexander, Nicola Filippini, James Kennedy, Stephen M SmithAbstract:Imaging studies in blind subjects have consistently shown that sensory and cognitive tasks evoke activity in the occipital cortex, which is normally visual. The precise areas involved and degree of activation are dependent upon the cause and age of onset of blindness. Here, we investigated the cortical language network at rest and during an auditory covert naming task in five bilaterally anophthalmic subjects, who have never received visual input. When listening to auditory definitions and covertly retrieving words, these subjects activated lateral occipital cortex bilaterally in addition to the language areas activated in sighted controls. This activity was significantly greater than that present in a control condition of listening to reversed speech. The lateral occipital cortex was also recruited into a left-lateralized resting-state network that usually comprises anterior and posterior language areas. Levels of activation to the auditory naming and reversed speech conditions did not differ in the calcarine (striate) cortex. This primary ‘visual’ cortex was not recruited to the left-lateralized resting-state network and showed high interhemispheric correlation of activity at rest, as is typically seen in unimodal cortical areas. In contrast, the interhemispheric correlation of resting activity in extrastriate areas was reduced in Anophthalmia to the level of cortical areas that are heteromodal, such as the inferior frontal gyrus. Previous imaging studies in the congenitally blind show that primary visual cortex is activated in higher-order tasks, such as language and memory to a greater extent than during more basic sensory processing, resulting in a reversal of the normal hierarchy of functional organization across ‘visual’ areas. Our data do not support such a pattern of organization in Anophthalmia. Instead, the patterns of activity during task and the functional connectivity at rest are consistent with the known hierarchy of processing in these areas normally seen for vision. The differences in cortical organization between bilateral Anophthalmia and other forms of congenital blindness are considered to be due to the total absence of stimulation in ‘visual’ cortex by light or retinal activity in the former condition, and suggests development of subcortical auditory input to the geniculo-striate pathway.
P. Calvas - One of the best experts on this subject based on the ideXlab platform.
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recessive and dominant mutations in retinoic acid receptor beta in cases with microphthalmia and diaphragmatic hernia
American Journal of Human Genetics, 2013Co-Authors: Myriam Srour, Nicolas Chassaing, David Chitayat, Veronique Caron, Pierre Bitoun, Lysanne Patry, Mariepierre Cordier, Josemario Capochichi, Christine Francannet, P. CalvasAbstract:Anophthalmia and/or microphthalmia, pulmonary hypoplasia, diaphragmatic hernia, and cardiac defects are the main features of PDAC syndrome. Recessive mutations in STRA6, encoding a membrane receptor for the retinol-binding protein, have been identified in some cases with PDAC syndrome, although many cases have remained unexplained. Using whole-exome sequencing, we found that two PDAC-syndrome-affected siblings, but not their unaffected sibling, were compound heterozygous for nonsense (c.355C>T [p.Arg119∗]) and frameshift (c.1201_1202insCT [p.Ile403Serfs∗15]) mutations in retinoic acid receptor beta (RARB). Transfection studies showed that p.Arg119∗ and p.Ile403Serfs∗15 altered RARB had no transcriptional activity in response to ligands, confirming that the mutations induced a loss of function. We then sequenced RARB in 15 subjects with Anophthalmia and/or microphthalmia and at least one other feature of PDAC syndrome. Surprisingly, three unrelated subjects with microphthalmia and diaphragmatic hernia showed de novo missense mutations affecting the same codon; two of the subjects had the c.1159C>T (Arg387Cys) mutation, whereas the other one carried the c.1159C>A (p.Arg387Ser) mutation. We found that compared to the wild-type receptor, p.Arg387Ser and p.Arg387Cys altered RARB induced a 2- to 3-fold increase in transcriptional activity in response to retinoic acid ligands, suggesting a gain-of-function mechanism. Our study thus suggests that both recessive and dominant mutations in RARB cause Anophthalmia and/or microphthalmia and diaphragmatic hernia, providing further evidence of the crucial role of the retinoic acid pathway during eye development and organogenesis.
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mutation analysis of the stra6 gene in isolated and non isolated Anophthalmia microphthalmia
Clinical Genetics, 2013Co-Authors: Nicolas Chassaing, Nicola K. Ragge, Ariana Kariminejad, A Buffet, J Martinovic, Siavash Ghaderisohi, P. CalvasAbstract:PDAC syndrome [Pulmonary hypoplasia/agenesis, Diaphragmatic hernia/eventration, Anophthalmia/microphthalmia (A/M) and Cardiac Defect] is a condition associated with recessive mutations in the STRA6 gene in some of these patients. Recently, cases with isolated Anophthalmia have been associated with STRA6 mutations. To determine the minimal findings associated with STRA6 mutations, we performed mutation analysis of the STRA6 gene in 28 cases with Anophthalmia. In 7 of the cases the Anophthalmia was isolated, in 14 cases it was associated with one of the major features included in PDAC and 7 had other abnormalities. Mutations were identified in two individuals: one with bilateral Anophthalmia and some features included in PDAC, who was a compound heterozygote for a missense mutation and a large intragenic deletion, and the second case with all the major features of PDAC and who had a homozygous splicing mutation. This study suggests that STRA6 mutations are more likely to be identified in individuals with A/M and other abnormalities included in the PDAC spectrum, rather than in isolated A/M cases.