Caracterización fenotípica de la retinitis pigmentaria asociada a sordera / Phenotypic characterization of retinitis pigmentosa associated with deafness

Introducción. El síndrome de Usher es una alteración genética caracterizada por la asociación de retinitis pigmentaria y sordera. Sin embargo, hay casos con familias en las cuales, a pesar de presentarse dicha asociación, no se puede diagnosticar un síndrome de Usher ni ninguno otro. Objetivo. Reevaluar fenotípicamente a 103 familias con diagnóstico previo de posible síndrome de Usher o retinitis pigmentaria asociada con sordera. Materiales y métodos. Se revisaron las historias clínicas de 103 familias con un posible diagnóstico clínico de síndrome de Usher o retinitis pigmentaria asociada con sordera. Se seleccionaron las familias cuyo diagnóstico clínico no correspondía a un síndrome de Usher típico. Los afectados fueron valorados oftalmológica y audiológicamente. Se analizaron variables demográficas y clínicas. Resultados. Se reevaluaron 14 familias cuyo diagnóstico clínico no correspondía al de síndrome de Usher. De las familias con diagnóstico inicial de síndrome de Usher típico, el 13,6 % recibieron uno posterior de "retinitis pigmentaria asociada con sordera" de "otro síntoma ocular asociado con hipoacusia',' o en forma aislada en una misma familia, de "retinitis pigmentaria" o "hipoacusia'.' Conclusiones. Es fundamental el estudio familiar en los casos en que la clínica no concuerda con el diagnóstico de síndrome de Usher típico. En los pacientes con retinitis pigmentaria asociada con sordera, el diagnóstico clínico acertado permite enfocar los análisis moleculares y, así, establecer un diagnóstico diferencial. Es necesario elaborar guías de nomenclatura en los casos con estos hallazgos atípicos para orientar a médicos e investigadores en cuanto a su correcto manejo.

Introduction: There are several syndromes that associate retinitis pigmentosa with deafness or hearing loss. The most frequent is Usher syndrome, a genetic disorder of autosomal recessive inheritance, which, in some cases, is accompanied by vestibular dysfunction. However, there are cases of families that despite having retinitis pigmentosa associated with deafness, cannot be classified as Usher or other syndromes due to additional findings. Objective: To reassess the phenotypes of 103 families previously diagnosed as possible Usher syndrome and/or retinitis pigmentosa associated with deafness. Materials and methods: We conducted a descriptive and retrospective study by reviewing the medical records of 103 families with a probable clinical diagnosis of Usher syndrome and/or retinitis pigmentosa associated with deafness. Families whose clinical diagnosis did not correspond to the typical Usher syndrome were selected and evaluated ophthalmologically and audiologically. Demographic and clinical variables were analyzed. Results: We selected and then reevaluated 14 families and 55 individuals as they did not correspond to a clinical diagnosis of Usher syndrome; 13.6% of the families initially considered to have typical Usher syndrome were later diagnosed with retinitis pigmentosa associated with deafness, another ocular symptom associated with hearing loss, retinitis pigmentosa, or isolated hearing loss in the same family. Conclusions: Family studies are essential in cases where the symptoms do not match the typical Usher' syndrome. In the cases of retinitis pigmentosa associated with deafness, a correct clinical diagnosis allows for focusing on the molecular analyses to establish a differential diagnosis. The need for nomenclature guidelines on these atypical findings is relevant to aid physicians and researchers in the best approach to these cases.

Genetic analysis and prenatal diagnosis of a Chinese pedigree affected with Usher syndrome due to novel compound heterozygous variants of PCDH15 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical features and genetic variant in a patient with Usher syndrome.@*METHODS@#Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus.@*RESULTS@#The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year.@*CONCLUSION@#The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.

Variation analysis of genes associated with Usher syndrome type 1 in 136 Chinese deafness families / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the variation of genes associated with Usher syndrome type 1(USH1)in 136 Chinese deafness families from Henan province. Methods: The data of 136 deafness families tested by next-generation sequencing(NGS) which identified in the center of genetics and prenatal diagnosis of the First Affiliated Hospital of Zhengzhou University from November 2016 to December 2019 were analysized and the variation frequency of six genes related to Usher syndrome type 1(MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2) were summarized. Results: Five deafness families were detected nine pathogenic or likely pathogenic variations in two genes, accounting for 3.7% of all families. Among them, four families were caused by MYO7A variations and one family was caused by CDH23 variation. Meanwhile, seven variations of two genes were reported for the first time. They were c.313delG, c.5257dupA, c.5435A>T, c.5636G>C, c.5722T>G of MYO7A, and c.155_166del, c.4802delA of CDH23. The patients' vision of family 2 and family 3 had no obvious abnormality at present, but according to genetic diagnosis and walking dealy, they were considered to be USH1. Conclusions: MYO7A is the most common caustive gene associated with USH1 in Henan deafness patients, the application of next-generation sequencing technology can make USH1 patients diagnosed earlier before the visual symptoms appear.

Analysis of pathogenic variants of USH2A gene in a child with Usher syndrome type II / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant in a child featuring Usher syndrome type II.@*METHODS@#Peripheral blood samples of the child and his parents were collected for the analysis of variants of hearing impairment-related genes. The findings were verified in 100 individuals with normal hearing.@*RESULTS@#The child was found to harbor compound heterozygous variants of the USH2A gene, namely c.8224-1G>C in intron 41 and c.5678C>G(p.Ser1893X) in exon 28, which were inherited respectively from his mother and father. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.8224-1G>C and c.5678C>G(p.Ser1893X) variants of USH2A gene were predicted to be pathogenic(PVS1+PM2+PM3).@*CONCLUSION@#The compound heterozygous variants c.8224-1G>C and c.5678C>G of the USH2A gene probably underlay the disease in this child. Above finding has enriched the spectrum of USH2A gene variants.

Genetic diagnosis of a pedigree affected with Usher syndrome type 1D/F / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with congenital sensorineural deafness.@*METHODS@#High-throughput sequencing was carried out to analyze the coding regions of 415 genes associated with hereditary deafness in the proband. Suspected variants were verified by PCR amplification and Sanger sequencing of her parents and sister.@*RESULTS@#The proband was found to have carried a heterozygous c.5131G>A (p.Val1711Ile) variant of the CDH23 gene and a heterozygous c.2884C>T(p.Arg962Cys) variant of the PCDH15 gene, which were respectively inherited from her mother and father. Her sister (with normal hearing) was also heterozygous for the c.5131G>A (p.Val1711Ile) variant of the CDH23 gene but not the c.2884C>T (p.Arg962Cys) variant of the PCDH15 gene. Based on the guidelines of the American College of Medical Genetics and Genomics, both variants were predicted to be likely pathogenic (PS1+PM2+PP3+PP4).@*CONCLUSION@#The c.5131G>A (p.Val1711Ile) variant of the CDH23 gene and c.2884C>T (p.Arg962Cys) variant of the PCDH15 gene probably underlay the pathogenesis of Usher syndrome type 1D/F in this pedigree.

Clinical phenotype and genotype analysis of the family with the Usher syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variants in a family affected with Usher syndrome type I, and analyze its genotype-phenotype correlation.@*METHODS@#Clinical data of the family was collected. Potential variants in the proband were detected by high-throughput sequencing. Suspected variants were verified by Sanger sequencing.@*RESULTS@#The proband developed night blindness at 10 year old, in addition with bilateral cataract and retinal degeneration. Hearing loss occurred along with increase of age. High-throughput sequencing and Sanger sequencing revealed that she has carried compound heterozygous variants of the MYO7A gene, namely c.2694+2T>G and c.6028G>A. Her sister carried the same variants with similar clinical phenotypes. Her daughter was heterozygous for the c.6028G>A variant but was phenotypically normal.@*CONCLUSION@#The clinical features and genetic variants were delineated in this family with Usher syndrome type I. The results have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

Caracterización clínica del síndrome de Usher. Provincia Holguín / Usher syndrome clinical characterization. Holguin province

Fundamento: El síndrome de Usher es una enfermedad determinada genéticamente, con una gran heterogeneidad clínica y genética; está caracterizada por hipoacusia neurosensorial de moderada a severa, retinosis pigmentaria progresiva y puede acompañarse de alteración vestibular. Por la alta prevalencia de esta enfermedad en la provincia de Holguín, se considera necesario este estudio. Objetivo: Caracterizar clínicamente todos los enfermos con diagnóstico clínico de síndrome de Usher en la provincia Holguín, en el período de enero del 2009 a enero del 2016. Metodología: Se realizó un estudio descriptivo, retrospectivo, tipo serie de casos, a los 53 pacientes con diagnóstico clínico de síndrome de Usher en la provincia Holguín. La muestra estuvo formada por los 53 enfermos residentes en la provincia. Se revisaron los registros del Centro Provincial de Retinosis Pigmentaria y las historias clínicas de estos pacientes; se recogieron los datos de interés en un instrumento que se confeccionó para ello. Las variables estudiadas fueron el sexo, la edad, edad del diagnóstico de la hipoacusia y severidad, edad del diagnóstico de la retinosis pigmentaria y los resultados de las pruebas audiológicas, lo que permitió conocer la función vestibular. Resultados: Se caracterizó clínicamente el 100 % de los enfermos estudiados. Predominó el sexo masculino (60,37 %). El 80 % presentó la retinosis pigmentaria en la primera infancia y la hipoacusia congénita profunda en 67,92 %. Las pruebas vestibulares demostraron que el 71,70 % presenta síndrome de Usher tipo II y el 28,30 % tiene el tipo I. Conclusiones: Predominó el sexo masculino, la hipoacusia precedió a la alteración visual. Se logró caracterizar clínicamente a estos afectados. Prevaleció el síndrome de Usher tipo II.

Background: Usher syndrome is a genetically determined disease with great clinical and genetic heterogeneity. This disease is characterized by sensorineural hearing loss of moderate to severe, progressive pigmentosa retinitis and may be accompanied by vestibular alteration. At the high prevalence of this disease in the province of Holguin, this study is considered necessary. Objective: To characterize all patients clinically with clinical diagnosis of Usher syndrome in Holguin province, in the period from January 2009 to January 2016. Methodology: A series types of retrospective cases, descriptive study with 53 patients with clinical diagnosis of Usher syndrome in Holguin province was conducted. The sample consisted of 53 patients residing in the province. Provincial records Pigmentosa Retinitis Pigmentosa Center and the medical records of these patients were reviewed, the data of interest are collected in an instrument that was drawn up for these. The variables studied were sex, age, age at diagnosis of hearing loss and severity, age of diagnosis of pigmentosa retinitis and the results of the audiological tests, allowing knowing the vestibular function. Results: It was possible to clinically characterize 100 % of the patients studied, predominantly male in a 60.37 %. 80 % had pigmentosa retinitis in early childhood and profound congenital hearing loss in 67.92 %. Vestibular tests showed that 71. 70 % have Usher syndrome type II and 28.30 % have the type I. Conclusions: mainly males, hearing loss preceded visual impairment. It was possible to clinically characterize those affected. It prevailed Usher syndrome type II.

Analysis of USH2A gene mutation in a Chinese family affected with Usher syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the disease-causing mutation in a Chinese family affected with Usher syndrome type II.</p><p><b>METHODS</b>All of the 11 members from the family underwent comprehensive ophthalmologic examination and hearing test, and their genomic DNA were isolated from venous leukocytes. PCR and direct sequencing of USH2A gene were performed for the proband. Wild type and mutant type minigene vectors containing exon 42, intron 42 and exon 43 of the USH2A gene were constructed and transfected into Hela cells by lipofectamine reagent. Reverse transcription (RT)-PCR was carried out to verify the splicing of the minigenes.</p><p><b>RESULTS</b>Pedigree analysis and clinical diagnosis indicated that the patients have suffered from autosomal recessive Usher syndrome type II. DNA sequencing has detected a homozygous c.8559-2A>G mutation of the USH2A gene in the proband, which has co-segregated with the disease in the family. The mutation has affected a conserved splice site in intron 42, which has led to inactivation of the splice site. Minigene experiment has confirmed the retaining of intron 42 in mature mRNA.</p><p><b>CONCLUSION</b>The c.8559-2A>G mutation in the USH2A gene probably underlies the Usher syndrome type II in this family. The splice site mutation has resulted in abnormal splicing of USH2A pre-mRNA.</p>

Identification of novel compound heterozygous mutations of USH2A gene in a family with Usher syndrome type II / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutations in a Chinese family with Usher syndrome type II.</p><p><b>METHODS</b>Genomic DNA was obtained from two affected and four unaffected members of the family and subjected to amplification of the entire coding sequence and splicing sites of USH2A gene. Mutation detection was conducted by direct sequencing of the PCR products. A total of 100 normal unrelated individuals were used as controls.</p><p><b>RESULTS</b>The patients were identified to be a compound heterozygote for two mutations: c.8272G>T (p.E2758X) in exon 42 from his mother and c.12376-12378ACT>TAA(p.T4126X) in exon 63 of the USH2A gene from his father. Both mutations were not found in either of the two unaffected family members or 100 unrelated controls, and had completely co-segregated with the disease phenotype in the family. Neither mutation has been reported in the HGMD database.</p><p><b>CONCLUSION</b>The novel compound heterozygous mutations c.8272G>T and c.12376-12378ACT>TAA within the USH2A gene may be responsible for the disease. This result may provide new clues for molecular diagnosis of this disease.</p>

Análisis Molecular de las Mutaciones 2299delG y C759F en Individuos Colombianos con Retinitis Pigmentosa e Hipoacusia Neurosensorial / Molecular analyses of 2299delG and C759F mutations in Colombian Retinitis Pigmentosa and Sensorineural hearing loss affected individuals

Determinar la presencia de las mutaciones 2299delG y C759F en 37 individuos colombianos no relacionados con asociación de RP e hipoacusia neurosensorial. Materiales y métodos: análisis de secuencia directa del exón 13 del gen USH2A en todos los individuos seleccionados para el estudio. Resultados: la mutación 2299delG fue observada únicamente en individuos con Síndrome de Usher tipo II, mientras que la mutación C759F, no fue observada en ninguno de los individuos del estudio...

To determine the presence of 2299delG and C759F mutations in 37 non-related subjects from Colombia suffering from RP and sensorineural deafness. Materials and methods: Exon 13 of USH2A gene was directly sequenced in all subjects selected for the study. Results: In this work, the 2299delG mutation was only observed in subjects suffering from Usher syndrome type II while the C759F mutation was not detected in any subject...

Pénfigo foliáceo variedad seborreica: reporte de un caso / Pemphigus foliaceus seborrheic variety: a case report / Pénfigo foliáceo variedade seborreica: relato de caso

El pénfigo eritematoso o seborréico, también denominado síndrome de Senear-Usher es la variedad leve y localizada del pénfigo foliáceo, de baja incidencia. La mayor parte de los casos se han reportado en adultos entre la segunda y tercera década de la vida, promedio de 54 años, sin predominio entre razas o sexo. Su etiología se debe a la presencia de anticuerpos anti IgG contra la desmogleina 1 de los queratinocitos de la capa granulosa. Clínicamente se presenta en forma de placas eritematoescamosas o eritematocostrosas bien definidas, de aspecto y distribución seborreica (cara, cuello y tronco), que se exacerban a la exposición solar. Su diagnóstico clínico puede ser difícil, ya que se superpone clínicamente con el lupus eritematoso discoide y la dermatitis seborreica, por lo cual es importante tenerlo en cuenta como diagnóstico diferencial en lesiones infiltradas en dorso nasal y región malar en patrón de alas de mariposa. Se presenta el caso clínico de un paciente con pénfigo foliáceo variedad seborreica una entidad de baja incidencia.

Pemphigus erythematosus or seborrheic, also called Senear - Usher syndrome,is a mild, localized variety of pemphigus foliaceus, an entity of low incidence. Most cases have been reported in adults between second and third decades of life, average 54 years, no difference between race or sex. Etiology is due to the presence of IgG antibodies against desmoglein 1 in keratinocytes of the granular layer. Clinically, defined erythematous plaques, seborrheic distribution aspect (face, neck and trunk), which are exacerbated by sun exposure. Clinical diagnosis can be difficult as clinically overlaps with discoid lupus erythematosus and seborrheic dermatitis. So, it is important to be considered as differential diagnosis in infiltrated nasal lesions, dorsum and malar region butterfly pattern. We report a case of pemphigus foliaceus- seborrheic variety, a low incidence entity.

O pênfigo eritematoso do tipo seborréico, também chamada de síndrome Senear -Usher é variedade leve e localizada do pênfigo foliáceo , de baixa incidência , a maioria dos casos foram relatados em adultos entre a segunda e terceira década de vida , com idade media de 54 anos, sem predominância entre raças ou sexo. A sua etiologia é devido à presença de anticorpos anti - IgG de desmogleína 1 dos queratinócitos da camada granular . Clinicamente, apresenta-se como placas eritematosas ou eritematocostrosas bem definidos, de aspecto e distribuição seborreica (face, pescoço e tronco), que são agravadas pela exposição ao sol. Seu diagnóstico clínico pode ser difícil, pois se sobrepõe clinicamente com lúpus eritematoso discóide e dermatite seborreica, por isso é importante te-lo em mente como diagnóstico diferencial nas lesões infiltradas no dorso da nariz e região malar com asas de borboleta. Apresenta-se o caso de um paciente com pênfigo foliáceo do tipo seborreico uma entidade de baixa incidência com poucos casos relatados na literatura.

Estudo clínico e padrão de herança em pacientes com retinose pigmentar / Clinical study and pattern of inheritance in patients with retinitis pigmentosa

OBJETIVO: Realizar análise epidemiológica de pacientes com retinose pigmentar (RP), caracterizando aspectos clínicos da doença e o padrão de herança encontrado em nosso meio, de acordo com a presença ou não de síndrome de Usher. MÉTODOS: Foram estudados 155 pacientes com RP, tendo sido a amostra dividida em 2 grupos: grupo 1 (n=130), com pacientes diagnosticados com RP clássica, sem associação com alterações sistêmicas; e grupo 2 (n=25), com pacientes diagnosticados com Síndrome de Usher (USH). Foram caracterizados aspectos clínicos da doença (sexo, idade, sintomas oculares, acuidade visual, alterações do segmento anterior e posterior e alterações em exames complementares) e o padrão de herança encontrado. Os dados foram obtidos através de anamnese, exame oftalmológico completo e exames subsidiários (campo visual manual, eletrorretinograma, retinografia simples e fluorescente), no período de fevereiro de 2003 a dezembro de 2009. Foi utilizado o programa SPSS versão 13.0 para análise dos dados estatísticos. RESULTADOS: A herança autossômica recessiva foi a forma mais comumente encontrada (76,2% no grupo 1), mas em proporção maior do que a de outros trabalhos da literatura. Um menor número de casos com padrão recessivo ligado ao X (1,5%) também foi notado no grupo 1. Não houve diferença estatisticamente significante entre as características clínicas entre os dois grupos. CONCLUSÃO: O padrão de herança encontrado nos pacientes com RP clássica foi similar ao encontrado em outros trabalhos. As características clínicas foram semelhantes nos dois grupos estudados.

OBJECTIVE: To make an epidemiological analysis of patients with retinitis pigmentosa (RP), characterizing clinical aspects of the disease and the pattern of inheritance found in the population studied, according to the presence or not of Usher Syndrome. METHODS: 155 patients with RP were studied and the sample was divided into two groups: group 1 (n = 130) with patients diagnosed with classical RP not associated with systemic symptoms; and group 2 (n = 25) with patients diagnosed with Usher syndrome (USH). We characterized clinical aspects of the disease (sex, age, ocular symptoms, visual acuity and anterior and posterior segment changes) and the pattern of inheritance. Data were obtained through medical history, complete ophthalmic examination and complementary exams (manual visual field, electroretinogram, retinography and fluorescent angiography) for the period of February 2003 to December 2009. We used SPSS version 13.0 for statistical data analysis. RESULTS: The autosomal recessive inheritance was the most commonly found (76.2% in group 1), but in greater proportion than that of other studies. A smaller number of cases with X-linked recessive pattern (1.5%) was also noted in group 1. There was no statistically significant difference between the clinical characteristics of the two groups. CONCLUSION: The pattern of inheritance found in patients with classical RP was similar to that found in other studies. Clinical characteristics were similar in both groups.

Nongranulomatous anterior uveitis in a patient with usher syndrome

A 34-year-old female with Usher syndrome, but no family history of similar illness, presented with complaints of vision reduction, redness, and photophobia. Biomicroscopic examination showed mildly injected conjunctivae bilateral, small, round keratic precipitates; bilateral +2 cells with no flare reaction in the anterior chamber; and bilateral posterior subcapsular cataracts. No associated posterior synechiae, angle neovascularization, or iris changes were detected; normal intraocular pressures were obtained. Fundus examination demonstrated waxy pallor of both optic nerves, marked vasoconstriction in retinal vessels, and retinal bone spicule pigment formation, with a normal macula. Electroretinography confirmed the diagnosis of retinitis pigmentosa, optical coherent tomography was normal and otolaryngology consultation was conducted. To our knowledge, an association between Usher syndrome and bilateral nongranulomatous anterior uveitis has not been previously reported, and our purpose is to report this association.

Comunicação em adultos surdocegos com síndrome de Usher: estudo observacional retrospectivo / Communication in deafblind adults with Usher syndrome: retrospective observational study

OBJETIVO: Conhecer as características e desafios enfrentados por surdocegos para comunicar-se e locomover-se; avaliar as repercussões da surdocegueira na vida dos sujeitos, especialmente em relação à comunicação e locomoção. MÉTODOS: Relato de série de casos realizado a partir de entrevistas semiestruturadas com questões relativas à funcionalidade da comunicação, com indivíduos com diagnóstico clínico de síndrome de Usher que frequentaram um ambulatório especializado em um serviço universitário, durante o ano de 2007. A amostra foi composta por 11 sujeitos surdocegos portadores da síndrome de Usher, com idades entre 20 e 57 anos (média de 43 anos e DP=12,27), dos quais 7 (63,6%) eram do gênero feminino. As respostas foram analisadas qualiquantitativamente pela técnica do Discurso do Sujeito Coletivo (DSC). RESULTADOS: Todos os entrevistados referiram que os sintomas visuais e auditivos tiveram início na infância. Dos 11 entrevistados, 6 sentiram que a doença afetou negativamente suas atividades cotidianas, 6 sentiram dificuldade no trabalho, 2 no lazer. Quatro relataram que houve mudança no relacionamento familiar e 5 relataram que não houve mudança na interação com a família e com os amigos. Na análise do discurso, quase 30% dos entrevistados relataram utilizar-se de formas alternativas de comunicação; 40% afirmaram deslocar-se sozinho se o trajeto for previamente conhecido. CONCLUSÃO: Os indivíduos com síndrome de Usher enfrentam situações desafiadoras nas atividades cotidianas, nos relacionamentos pessoais, no trabalho e no lazer. Formas alternativas de comunicação são muito utilizadas quando a comunicação oral não é possível. A maioria dos entrevistados referiu independência de locomoção, ou procurava alcançá-la.

PURPOSE: To characterize the communication and the main mechanisms that facilitate interpersonal relationships of deafblind, especially in relation to communication and locomotion and the impact of these aspects on deafblindness. METHODS: Report of a series of cases conducted from semi-structured interviews with questions relating to the functionality of communication, with Usher syndrome patients attended in a specialized clinic in a university service, in the year 2007. The sample consisted of 11 deafblind subjects, with Usher syndrome, aged between 20 and 57 years (mean age 43 years and SD=12.27), of which 7 (63.6%) were female. The responses were analyzed by qualitative-quantitative technique of the Discurso do Sujeito Coletivo (DSC). RESULTS: All participants reported that visual and auditory symptoms began in childhood. Of the 11 interviewed, 6 reported that the disease has negatively affected their daily activities, 6 experienced difficulty at work, and 2 at leisure. Four reported that there was a change in family relationships, and 5 reported no change in the interaction with family and friends. In discourse analysis, almost 30% of respondents reported to use alternative forms of communication, 40% said move alone if the way is known before. Only 1 of 11 participants said they did not ask for help when needed. CONCLUSION: Individuals diagnosed with Usher syndrome face challenging situations in daily activities, personal relationships, at work and at play. Alternative forms of communication are often used when verbal communication is not possible. The majority of respondents have independence of locomotion, or seeking ways to achieve it.

A Novel Frameshift Mutation of the USH2A Gene in a Korean Patient with Usher Syndrome Type II

Usher syndrome type II (USH2) is the most common form of Usher syndrome, characterized by moderate to severe hearing impairment and progressive visual loss due to retinitis pigmentosa. It has been shown that mutations in the USH2A gene are responsible for USH2. The authors herein describe a 34-year-old Korean woman with the typical clinical manifestation of USH2; she had bilateral hearing disturbance and progressive visual deterioration, without vestibular dysfunction. Molecular genetic study of the USH2A gene revealed a novel frameshift mutation (c.2310delA; Glu771LysfsX17). She was heterozygous for this mutation, and no other mutation was found in USH2A, suggesting the possibility of an intronic or large genomic rearrangement mutation. To the best of our knowledge, this is the first report of a genetically confirmed case of USH2 in Korea. More investigations are needed to delineate genotype-phenotype correlations and ethnicity-specific genetic background of Usher syndrome.

Molecular mechanisms underlying function of hair bundle: study on genetic deafness in mouse models / 生理学报

Although the basic principles for the function of peripheral auditory system have been known for many years, the molecular mechanisms which affect deafness are not clear. In recent years, the study of hereditary deafness associated mouse models has revealed the molecular basis which is related with the formation and function of the hair bundle and the mechanosensory organelle of hair cell. This review focused on the role of protein network, which is formed by the proteins encoded by the Usher syndrome type 1 genes, in hair-bundle development and mechanotransducer channel gating. And the review also showed how the stereocilia rootlets contribute to the hair bundle's mechanical properties and how the hair bundle produces suppressive masking. Finally, the review revealed multiple roles of the tectorial membrane and extracellular matrix in the hair bundles stimulating in the cochlea.

Aspectos médicos, genéticos y psicosociales del síndrome Usher / Medical, genetic, and psychosocial aspects of Usher´s syndrome

El síndrome Usher es una enfermedad genética, que se caracteriza por hipoacusia neurosensorial progresiva bilateral congénita, pérdida de visión debida a la retinosis pigmentaria y en ocasiones presenta también trastornos vestibulares. Objetivo: describir los principales aspectos médicos, genéticos y psicosociales presentes en los pacientes con síndrome Usher. Método: se realizó un estudio descriptivo transversal en 14 pacientes con diagnóstico de síndrome Usher atendidos en el Centro de Retinosis Pigmentaria de Camagüey, desde 1991 hasta 2008. Resultados: los 14 pacientes provenían de familias diferentes y seis de ellos tenían antecedentes patológicos familiares. Se encontró consanguinidad entre los padres de las personas afectadas en el 35,72 % de las familias, el principal grado de parentesco fue el de primos hermanos. El síndrome Usher tipo II fue la forma más frecuente. La mayoría de los pacientes eran procedentes de zonas urbanas; los que portaban el síndrome levemente aspiraban a alcanzar un mayor nivel de escolaridad, así como aquellos procedentes de las áreas urbanas. Tenían ocupación laboral nueve; algunos con trabajos riesgosos. De los nueve, cuatro no trabajaban y sólo dos eran del sexo femenino. Conclusiones: las manifestaciones clínicas del síndrome Usher provocan una doble limitación (visual y auditiva), que son responsables de los trastornos psicológicos y sociales que se asocian al mismo. Las personas afectadas necesitan de una atención especial que contribuya a mejorar la calidad de sus vidas.

Usher´s syndrome is a genetic disease that is characterized by congenital bilateral progressive neurosensory hypoacusis, loss of vision due to retinitis pigmentosa and occasionally also presents vestibular disorders. Objective: to describe the main medical, genetic, and psychosocial aspects present in patients with Usher´s syndrome. Method: a cross-sectional descriptive study was conducted in 14 patients with Usher´s syndrome diagnosis treated at the pigmentary retinosis Center in Camagüey, from 1991 to 2008. Results: fourteen patients came from different families and six of them had family pathological history. Found consanguinity among parents of persons affected by 35,72 % of families, cousins was the main degree of kinship. Usher´s syndrome type II was the most common form. The majority of patients were from urban areas; which carried the syndrome slightly aspired to achieve a higher level of schooling, as well as those from urban areas. Nine of them had jobs, some risky works. Four out of nine, did not work and only two were female. Conclusions: clinical manifestations of Usher´s syndrome cause a double constraint (visual and auditory), which are responsible for the psychological and social disorders that are associated to it. Affected persons need a special care to help improve the quality of their lives.

Comportamiento de la hipoacusia neurosensorial en niños / Behavior of neurosensory hypoacusis in children

La hipoacusia neurosensorial en el niño produce graves consecuencias en la adquisición del lenguaje, atributo importante para un aprendizaje y desempeño social adecuados. Objetivo: estudiar el comportamiento de la hipoacusia neurosensorial en niños en la provincia de Camagüey. Método: se realizó un estudio descriptivo sobre el comportamiento de la hipoacusia neurosensorial en niños de la provincia de Camagüey en el período comprendido de enero de 2007 a diciembre de 2009. El universo lo conformaron 250 niños hipoacúsicos y sordos, reportados por el centro de diagnóstico y orientación, la escuela de sordos e hipoacúsicos José María Heredia y la consulta de audiología del Hospital Pediátrico Universitario Eduardo Agramonte Piña. La aplicación de los criterios de exclusión determinó una muestra no probabilística de 83 niños. Las variables estudiadas fueron edad a la que se detectó el deterioro auditivo, sexo, causas, uni o bilateralidad, cuantía de la disfunción auditiva por audiometría liminar, electroaudiometría y potenciales auditivos evocados del tallo cerebral. Resultados: en el análisis de los resultados no existió predominio en el sexo, la edad a la que se diagnosticaron mayor número de pacientes fue de 0-5 años, en 43 pacientes. La categoría severa fue la pérdida auditiva más diagnosticada, en 31 enfermos y la profunda la menos, en sólo cinco pacientes; el sufrimiento fetal, neonato bajo peso, antimicrobianos ototóxicos y el síndrome de Usher fueron las causas más interrelacionadas. El sufrimiento fetal fue la causa de hipoacusia bilateral más frecuente.

Neurosensory hypoacusis in the child produces serious consequences in language acquisition, important attribute to appropriate learning and social performance. Objective: to study the behavior of neurosensory hypoacusis in children at Camagüey's province. Method: a descriptive study on the behavior of neurosensory hypoacusis in children at Camagüey's province was accomplished, from January 2007 to December 2009. The universe was constituted by 250 hypacusic children and deaf persons, reported by the Center for diagnosis and guidance, the deaf persons and hypacusic school José María Heredia and the audiology consultation at the University Paediatric Hospital Eduardo Agramonte Piña. The application of the exclusion criteria determined a non-probabilistic sample of 83 children. The studied variables were age at which hearing impairment was detected, sex, etiology, uni- or bilateralism, amount of auditory dysfunction by preliminary audiometry, electroaudiometry and auditory potentials evoked of the brainstem. Results: there was no predominance in sex in the analysis of results; the age in which a greater number of patients were diagnosed was 0-5 years, in 43 patients. Severe hearing loss was the most diagnosed, in 31 cases and in the deep one, just five patients; fetal distress, low birth weight, ototoxic antimicrobials and Usher's syndrome were the most interrelated causes. Fetal distress was the most frequent cause of bilateral hearing loss.

Síndrome de Usher de tipo II: caracterización oftalmológica, auditiva y genética de una familia consanguínea / Type II Usher syndrome: ophthalmological, auditory, and genetic characterization of a consanguineous family

Se caracterizó a una familia consanguínea de 25 miembros, 3 de los cuales padecían el síndrome de Usher de tipo II, a través del estudio auditivo, oftalmológico y genético en el Centro de Retinosis Pigmentaria de Santiago de Cuba. Los pacientes (2 varones y 1 fémina) tenían en común: aparición de la enfermedad en la etapa juvenil, mala visión nocturna, campos visuales reducidos, hipoacusia neurosensorial y resultados normales en las pruebas vestibulares; asimismo, en genética molecular, la electroforesis en gel de poliacrilamida reveló la presencia del marcador D1S237, estrechamente ligado al gen USH2 en el cromosoma 1. Esa caracterización permitirá aplicar la terapia génica y los implantes, tanto de células madre como cocleares, según corresponda.

A consanguineous family of 25 members, 3 of whom suffered from type II Usher syndrome was characterized through the auditory, ophthalmologic, and genetic study in the Retinitis Pigmentosa Center from Santiago de Cuba. The patients (2 males and a female) had in common: occurrence of the illness during youth, bad night vision, reduced visual fields, neurosensorial hypoakusia, and normal results in the vestibular tests; also, in molecular genetics, electrophoresis in polyacrilamide gel revealed the presence of the D1S237 marker, closely linked to the gene USH2 in chromosome 1. That characterization will allow to apply the genic therapy and both implants, mother cells and cochlear, as it corresponds.

Frecuencia de mutaciones en el gen de la usherina (USH2A) en 26 individuos colombianos con síndrome de Usher, tipo II / Mutational frequencies in usherin (USH2A gene) in 26 Colombian individuals with Usher syndrome type II

Introducción. El síndrome de Usher se caracteriza por hipoacusia neurosensorial congénita, retinitis pigmentaria y disfunción vestibular. Es la causa más frecuente de sordo-ceguera en el mundo. Se divide en tres tipos clínicos y doce subtipos genéticos. El tipo II es la forma más común y cerca de 80 % de los casos corresponden al subtipo 2 del síndrome de Usher. Objetivo. Establecer la frecuencia de mutaciones en la isoforma corta del gen USH2A en individuos colombianos con síndrome de Usher, tipo II. Materiales y métodos. Se estudiaron 26 individuos colombianos con diagnóstico clínico de síndrome de Usher, tipo II. Se hizo análisis de SSCP para los 20 exones que codifican para la isoforma corta y se secuenciaron los patrones anormales. Además, se secuenció el exón 13 en todos los individuos, ya que allí se encuentra la mutación más frecuente de este gen. Resultados. La mutación más frecuente es la c.2299delG, correspondiente al 27 % de la población. La segunda mutación identificada es la p.R334W, con una frecuencia de 15 %. Se identificó un nuevo cambio, el g.129G>T,en la región 5’UTR del gen, correspondiente al 4 % de la población. Se identificaron cuatro cambios polimórficos, uno de ellos es una deleción nueva identificada en el exón 20. Conclusiones. Se logró establecer que, al menos, 38 % de la población analizada con síndrome de Usher, tipo II, presenta alguna mutación en la isoforma corta del gen de la usherina. El diagnóstico molecular se logró establecer en el 23 %.

Introduction. Usher syndrome is a disorder characterized by progressive retinitis pigmentosa, prelingual sensory hearing loss and vestibular dysfunction. It is the most frequent cause of deaf-blindness in humans. Three clinical types and twelve genetic subtypes have been characterized. Type II is the most common, and among these cases, nearly 80% have mutations in the USH2A gene. Objective. The aim of the study was to establish the mutational frequencies for the short isoform of USH2A gene in Usher syndrome type II. Materials and methods. Twenty-six Colombian individuals with Usher syndrome type II were included. SSCP analysis for 20 exons of the short isoform was performed and abnormal patterns were sequenced. Sequencing of exon 13 of the USH2A gene was performed for all the individuals because the most frequent mutation is located in this exon. Results. The most frequent mutation was c.2299delG, identified in the 27% (n=8) of the sample. The second mutation, p.R334W, showed a frequency of 15%. A new variant identified in the 5’UTR region, g.129G>T, was present in 1 individual (4%). Four polymorphisms were identified; one of them is a new deletion in exon 20, first reported in this study. Conclusions. Mutations in the usherin short isoform were identified in 38% of a sample of 26 USH2 cases. Molecular diagnosis was established in 7 of the 26.