Visual experience shapes the Bouba-Kiki effect and the size-weight illusion upon sight restoration from congenital blindness.

The Bouba-Kiki effect is the systematic mapping between round/spiky shapes and speech sounds ("Bouba"/"Kiki"). In the size-weight illusion, participants judge the smaller of two equally-weighted objects as being heavier. Here we investigated the contribution of visual experience to the development of these phenomena. We compared three groups: early blind individuals (no visual experience), individuals treated for congenital cataracts years after birth (late visual experience), and typically sighted controls (visual experience from birth). We found that, in cataract-treated participants (tested visually/visuo-haptically), both phenomena are absent shortly after sight onset, just like in blind individuals (tested haptically). However, they emerge within months following surgery, becoming statistically indistinguishable from the sighted controls. This suggests a pivotal role of visual experience and refutes the existence of an early sensitive period: A short period of experience, even when gained only years after birth, is sufficient for participants to visually pick-up regularities in the environment, contributing to the development of these phenomena.

Narrativas de mães de crianças cegas congênitas sobre itinerários terapêuticos, arranjos de cuidados e experiências maternas: uma pesquisa no Instituto Benjamin Constant / Narratives of mothers of congenitally blind children on therapeutic pathways, care arrangements and maternal experiences: a study at the Benjamin Constant Institute

O objetivo da tese é analisar as narrativas de oito mães de crianças cegas congênitas, matriculadas no Instituto Benjamin Constant. O estudo abrange itinerários terapêuticos, arranjos de cuidados e experiências maternas. Utilizaram-se os postulados teóricos sobre narrativas de Ricoeur e a análise foi feita sob o marco teórico de Bardin. Optou-se pelo itinerário terapêutico como método de pesquisa, por valorizar as histórias de vidas das mães que participaram da pesquisa. A narrativa reforçou a utilização de metodologias participativas e inclusivas, baseadas no respeito, na solidariedade e na cooperação. As narrativas mostraram que as mães, após o primeiro itinerário, que é na maternidade, encontram na figura do médico pediatra o auxílio que as orienta sobre quais os itinerários a percorrer. Em seguida, elas procuram o oftalmologista, mais especificamente o retinólogo e, também, o neuropediatra. A chegada ao IBC acontece depois da confirmação derradeira da cegueira do filho. As mães das crianças e adolescentes matriculados no IBC permanecem no espaço do Instituto, diariamente, enquanto seus filhos estão em aula ou em algum atendimento. Essa permanência se justifica por razão da distância entre o IBC e suas casas. A espera permite compartilharem, com outras mães, situações vivenciadas para o fortalecimento de vínculos de afetos, mas também existem tensões. O estudo apontou, ainda, que o discurso iatrogênico, com palavras ou ações de alguns médicos, causou ansiedade, desconfiança, confusão e sentimento de desrespeito. Outro dado relevante, encontrado por meio das narrativas, foi a dificuldade que encontraram ao transitarem nos espaços públicos com seus filhos, por causa de barreiras atitudinais. Ainda segundo as narrativas, o cuidado que elas dispensam quase que integralmente aos seus filhos (as), apesar de toda a sobrecarga que relatam, não é considerado um trabalho, pelo fato de não ser remunerado. As mães entendem que a tarefa de cuidar é um ato de amor para com o filho e, não, um trabalho. Por fim, a pesquisa também investigou os impactos que a pandemia de COVID 19 ocasionou nas vidas das mães e de seus filhos, surgindo como principais desafios o afastamento do espaço da escola e o manejo das aulas on-line. (AU)

The objective of the thesis is to study the narratives of eight mothers of congenitally blind children enrolled at the Benjamin Constant Institute. The study covers therapeutic journeys, care arrangements, and maternal experiences. Theoretical postulates on narratives by Ricoeur were utilized, and the analysis was conducted within the theoretical framework of Bardin. The therapeutic journey was chosen as the research method, as it values the life stories of the participating mothers. The narrative reinforced the use of participatory and inclusive methodologies based on respect, solidarity, and cooperation. The narratives showed that mothers, after the initial journey in maternity, seek guidance from pediatricians on the paths to take. They then consult ophthalmologists, specifically retinologists, and neuropediatricians. Arrival at the IBC occurs after the final confirmation of the child's blindness. Mothers of children and adolescents enrolled at the IBC stay at the Institute daily while their children are in class or receiving some form of assistance. This stay is due to the distance between the IBC and their homes. Waiting allows them to share experiences with other mothers, strengthening emotional bonds, but tensions also exist. The study also pointed out that iatrogenic discourse, with words or actions from some doctors, caused anxiety, mistrust, confusion, and feelings of disrespect. Another significant finding from the narratives was the difficulty they encountered when navigating public spaces with their children due to attitudinal barriers. According to the narratives, the care they provide to their children, despite the reported burden, is not considered work because it is unpaid. Mothers view caregiving as an act of love for their children, not as a job. Finally, the research also investigated the impacts of the COVID-19 pandemic on the lives of the mothers and their children, with the main challenges being the separation from the school environment and the management of online classes. (AU)

Long-Term Anatomic and Visual Outcomes of Planned Preterm Delivery and Treatment of Norrie Disease.

We previously reported that planned preterm delivery at 34 weeks gestational age provided an opportunity to treat Norrie disease in the vasoproliferative phase, prevented infantile retinal detachment, and preserved functional vision without further treatment after infancy. Although retinal vascularization did not proceed postnatally, after 8 years of follow-up, the retinas remained attached, and rudimentary foveal development was observed by optical coherence tomography. Best corrected visual acuity gradually improved to 20/80 with both eyes, and visual fields and real-world visual performance were remarkably functional. Global development progressed appropriately, and no long-term sequelae of premature delivery were observed. [Ophthalmic Surg Lasers Imaging Retina 2022;53:464-467.].

A novel frameshift c.22_25dupGCAT mutation of the NDP gene in a Chinese infant with Norrie disease: A case report.

RATIONALE: Norrie disease (ND) is a rare X-linked recessive disease characterized by bilateral congenital blindness and auditory impairments. According to the previous studies, Norrin cystine knot growth factor (NDP) gene have been found to be responsible for ND. Herein, we report a case of ND with a novel mutation in NDP and elucidate the clinical and molecular characteristics of this patient. PATIENT CONCERNS: A 2-month-old Chinese male infant presented with gray-white opacification in the bilateral cornea. Vitreous opacity and retinal detachment were observed on ocular ultrasound. Furthermore, a novel de novo hemizygous mutation (c.22_25dupGCAT, p.S9Cfs∗18) in exon 2 of the NDP gene was identified by next-generation sequencing. SWISS-MODEL predicted that the c.22_25dupGCAT mutation truncated the NDP protein. DIAGNOSIS: Based on the above clinical and genetic evidence, this patient was eventually diagnosed with ND. INTERVENTIONS: Currently, no clinical therapy is available for ND. OUTCOMES: In addition to the typical ocular symptoms, no other abnormalities were observed. The patient's vital signs remained stable and normal. LESSON: A novel causative mutation of NDP was identified using next-generation sequencing. Our report expands the pathogenic mutation spectrum of NDP and facilitates genetic counseling and prenatal diagnosis. Additionally, we emphasize the importance of molecular genetic testing in the diagnosis of ND.

Da disfagia à restrição alimentar: efeitos das dificuldades de adaptação parental à filha com cegueira congênita / From dysphagia to food restriction: effects of parental adaptation to the daughter with congenital blindness / De la disfagia a la restricción alimentaria: efectos de las dificultades de adaptación de los padres a la hija con ceguera congénita

Introdução: O nascimento de um filho com deficiência pode alterar rotinas e influenciar no processo de adaptação dos pais, por se caracterizar como um acontecimento não esperado. Ainda pode produzir nos progenitores sentimentos semelhantes aos vivenciados em um processo de luto. Objetivo: Analisar a relação entre a adaptação parental à filha com cegueira congênita e disfagia, relacionadas à prematuridade extrema, e seu possível impacto no processo de adesão às orientações terapêuticas sobre a alimentação da criança. Método: Trata-se de um estudo de caso de cunho qualitativo. Foi realizada uma análise da adaptação parental à deficiência, e avaliações fonoaudiológicas da linguagem e da disfagia. Resultados: A avaliação fonoaudiológica evidenciou disfagia para líquidos finos e ausência de alterações de linguagem. A restrição alimentar tornou-se evidente a partir da dificuldade parental em aceitar e seguir as orientações quanto à consistência alimentar. A análise dos dados de adaptação parental à deficiência da filha sugere que essa dificuldade esteve relacionada à aceitação da cegueira e da disfagia. A emergência de restrição alimentar esteve relacionada às dificuldades na aceitação das orientações fonoaudiológicas por parte dos pais, considerando a disfagia para líquidos finos. Essas dificuldades encontram um correlato na análise da adaptação parental do pai e da mãe. Conclusão: Evidencia-se a importância do acompanhamento por uma equipe interdisciplinar.

Introduction: The birth of a child with a disability can change routines and influence the parents' adaptation process, as it is characterized as an unexpected event. It can still produce similar feelings in parents as those experienced in a grieving process. Objective: To analyze the relationship between parental adaptation to the daughter with congenital blindness and dysphagia, related to extreme prematurity, and its possible impact on the process of adherence to therapeutic guidelines on child nutrition. Method: This is a qualitative case study. An analysis of parental adaptation to disability as well as language therapy assessments of language and dysphagia were performed. Results: The speech therapy evaluation showed dysphagia for fine liquids and absence of language disorders. Dietary restriction became evident from the parental difficulty in accepting and following the guidelines regarding food consistency. The analysis of the parental adaptation data to the daughter's disability suggests that this difficulty was related to the acceptance of blindness and dysphagia. The emergence of food restriction was related to the difficulties in parents' acceptance of speech therapy guidelines, considering dysphagia for thin liquids. These difficulties find a correlate in the analysis of the father and mother's parental adaptation. Conclusion: The importance of monitoring by an interdisciplinary team is evident.

Introducción: El nacimiento de un niño con discapacidad puede cambiar las rutinas y estilos de vida de los padres, ya que se caracteriza por ser un evento inesperado. Todavía puede producir sentimientos similares en los padres a los que experimentaron en un proceso de duelo. Objetivo: Analizar la relación entre la adaptación de los padres a la hija con ceguera congénita y disfagia, relacionada con la prematuridad extrema, y ​​su posible impacto en el proceso de adherencia a las guías terapéuticas en nutrición infantil. Método: Este es un estudio de caso cualitativo. Se realizó un análisis de la adaptación de los padres a la discapacidad y la evaluación del habla y el lenguaje de la disfagia. Resultados: La evaluación de logopedia mostró disfagia por líquidos finos y ausencia de trastornos del lenguaje. La restricción dietética se hizo evidente por la dificultad de los padres para aceptar y seguir las pautas con respecto a la consistencia de los alimentos. El análisis de los datos de adaptación de los padres a la discapacidad de la hija sugiere que esta dificultad estaba relacionada con la aceptación de la ceguera y la disfagia. La aparición de la restricción alimentaria se relacionó con las dificultades en la aceptación por parte de los padres de las pautas de logopedia, considerando la disfagia por líquidos diluidos. Estas dificultades encuentran correlación en el análisis de la adaptación parental del padre y la madre. Conclusión: Es evidente la importancia del seguimiento por parte de un equipo interdisciplinario.

Identification of a variant in NDP associated with X-linked retinal dysplasia in the English cocker spaniel dog.

PURPOSE: Three related male English Cocker Spaniels (ECS) were reported to be congenitally blind. Examination of one of these revealed complete retinal detachment. A presumptive diagnosis of retinal dysplasia (RD) was provided and pedigree analysis was suggestive of an X-linked mode of inheritance. We sought to investigate the genetic basis of RD in this family of ECS. METHODS: Following whole genome sequencing (WGS) of the one remaining male RD-affected ECS, two distinct investigative approaches were employed: a candidate gene approach and a whole genome approach. In the candidate gene approach, COL9A2, COL9A3, NHEJ1, RS1 and NDP genes were investigated based on their known associations with RD and retinal detachment in dogs and humans. In the whole genome approach, affected WGS was compared with 814 unaffected canids to identify candidate variants, which were filtered based on appropriate segregation and predicted pathogenic effects followed by subsequent investigation of gene function. Candidate variants were tested for appropriate segregation in the ECS family and association with disease was assessed using samples from a total of 180 ECS. RESULTS: The same variant in NDP (c.653_654insC, p.Met114Hisfs*16) that was predicted to result in 15 aberrant amino acids before a premature stop in norrin protein, was identified independently by both approaches and was shown to segregate appropriately within the ECS family. Association of this variant with X-linked RD was significant (P = 0.0056). CONCLUSIONS: For the first time, we report a variant associated with canine X-linked RD. NDP variants are already known to cause X-linked RD, along with other abnormalities, in human Norrie disease. Thus, the dog may serve as a useful large animal model for research.

Norrie disease with a spontaneously shrinking choroid plexus abnormality: a case report.

Background: Norrie disease is a genetic disorder of the retina characterized by impaired retinal vascular development leading to retinal detachment and blindness. Non-retinal manifestations of the disorder include intellectual disability and seizure disorders. However, to date, no association with neurological mass lesions has been described.Materials and methods: Case reporResults: Here, we report a case of a patient with Norrie disease who presented with an enhancing mass of the choroid plexus that spontaneously diminished in size. Conclusion: This report suggests watchful waiting as a reasonable clinical approach to choroid plexus lesions in patients with Norrie disease.

Severe reflux esophagitis and multiple congenital defects: A case report.

INTRODUCTION: Gastroesophageal reflux disease is a common and troublesome condition. This paper reports a rare case of gastroesophageal reflux disease caused by ectopic biliary drainage accompanying the absence of a pyloric channel and duodenal bulb in a female patient with multiple underlying malformations. PATIENT CONCERNS: A 24-year-old female presented with acid regurgitation and abdominal pain for one month. She was born two weeks premature and with blindness of the right eye. Cardiac murmur was detected in the physical examination. DIAGNOSIS: Gastroendoscopy was performed, and a class D reflux esophagitis and ectopic papilla complicated with the absence of a pyloric channel and duodenal bulb were found. Doppler echocardiography further confirmed the defects of atrial and ventricular septa. Trio-based whole exome sequencing was performed on the proband and her family to find the potential association of multiple variations. However, no putative pathogenic mutations were found. INTERVENTIONS: The patient received proton pump inhibitors and prokinetic treatment and underwent surgical repair of septal defects. OUTCOMES: The symptoms were quickly relieved, and the patient was kept stable upon follow-up. CONCLUSION: The combination of an absent pylorus and ectopic papilla is a rare cause of reflux esophagitis. Unusual gastrointestinal anatomical variations may be accompanied by other malformations. Though no remarkable mutation were detected in this case, sequencing is an efficient technique worth full consideration.

A novel c.287G>T NDP missense mutation in a Chinese family with Norrie disease.

BACKGROUND: Norrie disease is a rare X-linked recessive disorder in affected males. The typical features are congenital blindness, progressive hearing impairment, and, in some cases, some degree of mental retardation, microphthalmia, microcornea, growth failure, and seizures. Norrie disease is caused by mutations in the Norrie disease pseudoglioma gene (NDP), which encodes the Norrin protein that plays a crucial role in vascular development, neural cell differentiation, and proliferation in the retina and cerebellum. The aim of the present study was to identify the genetic cause of the disease and the phenotypic characteristics of the patients in an affected Chinese family. MATERIALS AND METHODS: A Chinese family with Norrie disease was studied, and clinical phenotypes of the proband were observed. With informed consent from the patients' family, blood samples from family members were collected, genomic DNA was extracted, and Sanger sequencing was performed to identify the disease-causing mutation. RE: sults: The c.287 G > T mutation of NDP was identified by Sanger sequencing and resulted in p.Cys96Phe. The pathogenicity prediction was performed by MutationTaster, Polyphen-2, SIFT, and PROVEAN, all of which suggested that the mutation is disease-causing and may be responsible for the phenotypes of Norrie disease. CONCLUSION: The c.287 G > T of NDP is a novel mutation responsible for Norrie disease in a Chinese family.

Auditory Input and Postural Control in Adults: A Narrative Review.

Importance: An increase in the number of mechanistic studies targeting the association between sound and balance has been observed in recent years, but their results appear equivocal. Observations: A search of PubMed and the Cochrane Database of Systematic Reviews for English-language studies on auditory input and postural control published from database inception through October 31, 2019, yielded 28 articles for review. These articles included 18 (64%) studies of healthy adults, 1 (4%) of participants with Alzheimer disease, 2 (7%) of participants with congenital blindness, 3 (11%) of participants with vestibular loss, and 4 (14%) of participants with diverse levels of hearing loss. Studies varied by the type of audio stimuli (natural vs generated sounds), apparatus (speakers vs headphones), and movement of sounds (eg, stationary, rotational). Most balance measurements involved standing on the floor or foam with eyes open or closed during which sway amount or velocity was quantified. Stationary broadband sounds, including white or environmental noise, may improve balance, but the results regarding stationary pure tone were inconclusive. The implication of moving sounds varied by apparatus (typically destabilizing when headphones were used) and sensory loss (more destabilizing with vestibular or hearing loss but perhaps less with a unilateral cochlear implant). Conclusions and Relevance: Findings from this review suggest that stationary broadband noise can serve as an auditory anchor for balance primarily when projected via speakers and when the balance task is challenging. More research is needed that includes individuals with sensory loss and that tests paradigms using dynamic, ecologically valid sounds; clinicians should also consider auditory cues and the presence of hearing loss in balance and fall-risk assessments.

Attitudes of people with inherited retinal conditions toward gene editing technology.

BACKGROUND: The views of people with genetic conditions are crucial to include in public dialogue around developing gene editing technologies. This qualitative study sought to characterize the attitudes of people with inherited retinal conditions (retinitis pigmentosa [RP] and Leber congenital amaurosis [LCA]) toward gene editing. METHODS: Individuals with RP (N = 9) and LCA (N = 8) participated in semi-structured qualitative interviews about their experience with and attitudes toward blindness, and their views about gene editing technology for somatic, germline, and enhancement applications. RESULTS: Participants saw potential benefits from gene editing in general, but views about its use for retinal conditions varied and were influenced by personal perspectives on blindness. Those who felt more negatively toward blindness, particularly those with later onset blindness, were more supportive of gene editing for retinal conditions. Concerns about both germline and somatic editing included: the importance of informed consent; impacts of gene editing on social attitudes and barriers affecting blind people; and worries about "eliminating" blindness or other traits. CONCLUSION: People with RP and LCA have diverse attitudes toward gene editing technology informed by their own lived experience with disability, and many have concerns about how the ways in which it is discussed and implemented might affect them.

Gene Augmentation and Readthrough Rescue Channelopathy in an iPSC-RPE Model of Congenital Blindness.

Pathogenic variants of the KCNJ13 gene are known to cause Leber congenital amaurosis (LCA16), an inherited pediatric blindness. KCNJ13 encodes the Kir7.1 subunit that acts as a tetrameric, inwardly rectifying potassium ion channel in the retinal pigment epithelium (RPE) to maintain ionic homeostasis and allow photoreceptors to encode visual information. We sought to determine whether genetic approaches might be effective in treating blindness arising from pathogenic variants in KCNJ13. We derived human induced pluripotent stem cell (hiPSC)-RPE cells from an individual carrying a homozygous c.158G>A (p.Trp53∗) pathogenic variant of KCNJ13. We performed biochemical and electrophysiology assays to confirm Kir7.1 function. We tested both small-molecule readthrough drug and gene-therapy approaches for this "disease-in-a-dish" approach. We found that the LCA16 hiPSC-RPE cells had normal morphology but did not express a functional Kir7.1 channel and were unable to demonstrate normal physiology. After readthrough drug treatment, the LCA16 hiPSC cells were hyperpolarized by 30 mV, and the Kir7.1 current was restored. Similarly, we rescued Kir7.1 channel function after lentiviral gene delivery to the hiPSC-RPE cells. In both approaches, Kir7.1 was expressed normally, and there was restoration of membrane potential and the Kir7.1 current. Loss-of-function variants of Kir7.1 are one cause of LCA. Using either readthrough therapy or gene augmentation, we rescued Kir7.1 channel function in iPSC-RPE cells derived from an affected individual. This supports the development of precision-medicine approaches for the treatment of clinical LCA16.

Repair of Total Tractional Retinal Detachment in Norrie Disease: Report of Technique and Successful Surgical Outcome.

CASE REPORT: Norrie disease is a rare, but devastating cause of pediatric retinal detachment, universally portending a poor visual prognosis. This paper describes successful surgical management of an infant with total retinal detachment associated with Norrie disease mutation. The infant was a full-term white male who presented with bilateral total funnel retinal detachments (RDs). He underwent genetic testing, which demonstrated single-point mutation 133 G>A transition in exon 2 of the NDP gene. The retinal detachment was managed with translimbal iridectomy, lensectomy, capsulectomy, and vitrectomy. Careful dissection of the retrolental membranes resulted in opening of the funnel. Single-stage surgery in this child's eye achieved re-attachment of the posterior pole with progressive reabsorption of subretinal fluid and cholesterol without the need for external drainage. Fluorescein angiography, performed at 2 months postoperatively, demonstrated perfusion of major vascular arcades, but with significant abnormalities and aneurysmal changes of higher-order vessels, suggestive of retinal and vascular dysplasia. The child has maintained brisk light perception vision. Early surgical intervention with careful dissection of tractional tissues can potentially result in good anatomic outcomes in some patients with Norrie disease-associated retinal detachment. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:260-262.].

Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina.

Loss of photoreceptors is a common endpoint in degenerative retinal diseases. Human pluripotent stem cells provide a potential source for photoreceptor replacement, but, even in mouse models, the efficiency and efficacy of transplantation-based repair remains poor. In this study, we examined the degree to which immune rejection contributes to these disappointing outcomes using an immunodeficient IL2 receptor γ (IL2rγ)-null mouse model. Our results show that prevention of cell rejection in the normal and degenerating retinal environment significantly improves long-term survival and integration of hESC-derived donor retinal cells. Transplanted cells are able to differentiate into mature photoreceptors expressing various opsins and can functionally integrate into congenitally blind mice. Our work suggests that even though the retina is often considered immune-privileged, suppression of host immune-mediated cell rejection may well be a useful approach for improving long-term integration of transplanted cells with a view to successful clinical outcomes.

Sight restoration after congenital blindness does not reinstate alpha oscillatory activity in humans.

Functional brain development is characterized by sensitive periods during which experience must be available to allow for the full development of neural circuits and associated behavior. Yet, only few neural markers of sensitive period plasticity in humans are known. Here we employed electroencephalographic recordings in a unique sample of twelve humans who had been blind from birth and regained sight through cataract surgery between four months and 16 years of age. Two additional control groups were tested: a group of visually impaired individuals without a history of total congenital blindness and a group of typically sighted individuals. The EEG was recorded while participants performed a visual discrimination task involving intact and scrambled biological motion stimuli. Posterior alpha and theta oscillations were evaluated. The three groups showed indistinguishable behavioral performance and in all groups evoked theta activity varied with biological motion processing. By contrast, alpha oscillatory activity was significantly reduced only in individuals with a history of congenital cataracts. These data document on the one hand brain mechanisms of functional recovery (related to theta oscillations) and on the other hand, for the first time, a sensitive period for the development of alpha oscillatory activity in humans.

Bilateral persistent fetal vasculature due to a mutation in the Norrie disease protein gene.

We report a case of a 7-week-old boy with bilateral leukocoria and asymmetric microphthalmia who was found to have Norrie disease. Symmetrically hyperdense globes with no evidence of calcification were seen on CT scan. The MRI showed bilateral retinal hemorrhages resulting in conical vitreous chambers-narrow at the optic disc and widened toward the lens-characteristic of persistent fetal vasculature. Genetic evaluation revealed a previously undescribed mutation in the Norrie disease protein gene.

"Visual" Cortex of Congenitally Blind Adults Responds to Syntactic Movement.

Human cortex is comprised of specialized networks that support functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity offer unique insights into this question. In congenitally blind individuals, "visual" cortex responds to auditory and tactile stimuli. Remarkably, recent evidence suggests that occipital areas participate in language processing. We asked whether in blindness, occipital cortices: (1) develop domain-specific responses to language and (2) respond to a highly specialized aspect of language-syntactic movement. Nineteen congenitally blind and 18 sighted participants took part in two fMRI experiments. We report that in congenitally blind individuals, but not in sighted controls, "visual" cortex is more active during sentence comprehension than during a sequence memory task with nonwords, or a symbolic math task. This suggests that areas of occipital cortex become selective for language, relative to other similar higher-cognitive tasks. Crucially, we find that these occipital areas respond more to sentences with syntactic movement but do not respond to the difficulty of math equations. We conclude that regions within the visual cortex of blind adults are involved in syntactic processing. Our findings suggest that the cognitive function of human cortical areas is largely determined by input during development. SIGNIFICANCE STATEMENT: Human cortex is made up of specialized regions that perform different functions, such as visual motion perception and language processing. How do genes and experience contribute to this specialization? Studies of plasticity show that cortical areas can change function from one sensory modality to another. Here we demonstrate that input during development can alter cortical function even more dramatically. In blindness a subset of "visual" areas becomes specialized for language processing. Crucially, we find that the same "visual" areas respond to a highly specialized and uniquely human aspect of language-syntactic movement. These data suggest that human cortex has broad functional capacity during development, and input plays a major role in determining functional specialization.

Identification and Functional Analysis of a Novel MIP Gene Mutation Associated with Congenital Cataract in a Chinese Family.

Congenital cataracts are major cause of visual impairment and blindness in children and previous studies have shown about 1/3 of non-syndromic congenital cataracts are inherited. Major intrinsic protein of the lens (MIP), also known as AQP0, plays a critical role in transparency and development of the lens. To date, more than 10 mutations in MIP have been linked to hereditary cataracts in humans. In this study, we investigated the genetic and functional defects underlying a four-generation Chinese family affected with congenital progressive cortical punctate cataract. Mutation screening of the candidate genes revealed a missense mutation at position 448 (c.448G>C) of MIP, which resulted in the substitution of a conserved aspartic acid with histidine at codon 150 (p.D150H). By linkage and haplotype analysis, we obtained positive multipoint logarithm of odds (LOD) scores at microsatellite markers D12S1632 (Zmax = 1.804 at α = 1.000) and D12S1691 (Zmax = 1.806 at α = 1.000), which flanked the candidate locus. The prediction results of PolyPhen-2 and SIFT indicated that the p.D150H mutation was likely to damage to the structure and function of AQP0. The wild type and p.D150H mutant AQP0 were expressed in HeLa cells separately and the immunofluorescence results showed that the WT-AQP0 distributed at the plasma membrane and in cytoplasm, while AQP0-D150H failed to reach the plasma membrane and was mainly retained in the Golgi apparatus. Moreover, protein levels of AQP0-D150H were significantly lower than those of wide type AQP0 in membrane-enriched lysates when the HEK-293T cells were transfected with the same amount of wild type and mutant plasmids individually. Taken together, our data suggest the p.D150H mutation is a novel disease-causing mutation in MIP, which leads to congenital progressive cortical punctate cataract by impairing the trafficking mechanism of AQP0.

Olfactory Function Assessment of Blind Subjects Using the Sniffin' Sticks Test.

OBJECTIVE: In recent years, a growing number of studies have focused on the olfactory abilities of blind individuals as well as their tactile and auditory senses. In this study, we aimed to investigate possible alterations in the sense of smell in early- and late-blind subjects as compared with sighted controls, using a Sniffin' Sticks test battery. STUDY DESIGN: Prospective clinical study. SETTING: Tertiary referral center. SUBJECTS AND METHODS: A total of 66 subjects were included in the study. The subjects were divided into 2 groups: blind subjects-who were then subgrouped as subjects with congenital blindness (n = 17) and those with acquired blindness (n = 16)-and sighted subjects (n = 33). We compared both congenitally and acquired blind subjects with sighted counterparts using the Sniffin' Sticks test for odor threshold, odor discrimination, odor identification, and total odor scores. RESULTS: The blind subjects were more successful than their sighted counterparts in odor discrimination and odor threshold tasks. There was no statistically significant difference between the blind participants and the sighted individuals in terms of odor identification value. Another important finding was that the difference between individuals with congenital blindness and those with acquired blindness was not significant in any of the parameters. CONCLUSION: This finding may suggest that odor discrimination and odor threshold in blind people were superior to those of controls. There was no difference in any of the results of tasks among congenital and acquired blind subjects.