Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.561
Filtrar
1.
AJNR Am J Neuroradiol ; 42(2): 377-381, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33509916

RESUMO

BACKGROUND AND PURPOSE: Imaging is fundamental to assessing the acoustic pathway in infants with congenital deafness. We describe our depiction of the membranous labyrinth in infants using the heavily T2-weighted 3D FLAIR sequence without a contrast agent. MATERIALS AND METHODS: We retrospectively reviewed 10 infants (20 ears) (median term equivalent age: 2 weeks; IQR: 1-5 weeks) who had undergone brain MR imaging including a noncontrast heavily T2-weighted 3D FLAIR scan of the temporal bone. For each ear, 3 observers analyzed, in consensus, the saccule, the utricle, and the 3 ampullae, assessing the visibility (score 0, not appreciable; score 1, visible without well-defined boundaries; score 2, visible with well-defined boundaries) and morphology ("expected" or "unexpected" compared with adults). The heavily T2-weighted 3D FLAIR sequence was scored for overall quality (score 0, inadequate; score 1, adequate but with the presence of image degradation; score 2, adequate). RESULTS: Six (60%) MR examinations were considered adequate (score 1 or 2). The saccule was visible in 10 ears (83.3%) with an expected morphology in 9 ears (90%). In 1 ear of an infant with congenital deafness, the saccule showed an unexpected morphology. The utricle was visible as expected in 12 ears (100%). The lateral ampulla was visible in 5 ears (41.6%), the superior ampulla was visible in 6 ears (50.0%), and the posterior ampulla was visible in 6 ears (50.0%), always with expected morphology (100%). CONCLUSIONS: MR imaging can depict the membranous labyrinth in infants using heavily T2-weighted 3D FLAIR without an injected contrast agent, but the sequence acquisition time reduces its feasibility in infants undergoing MR studies during natural sleep.


Assuntos
Surdez/diagnóstico por imagem , Orelha Interna/diagnóstico por imagem , Imageamento Tridimensional/métodos , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Meios de Contraste/administração & dosagem , Surdez/congênito , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Recém-Nascido , Masculino , Estudos Retrospectivos
2.
PLoS One ; 15(7): e0233582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735620

RESUMO

The craniofacial developmental disorder Burn-McKeown Syndrome (BMKS) is caused by biallelic variants in the pre-messenger RNA splicing factor gene TXNL4A/DIB1. The majority of affected individuals with BMKS have a 34 base pair deletion in the promoter region of one allele of TXNL4A combined with a loss-of-function variant on the other allele, resulting in reduced TXNL4A expression. However, it is unclear how reduced expression of this ubiquitously expressed spliceosome protein results in craniofacial defects during development. Here we reprogrammed peripheral mononuclear blood cells from a BMKS patient and her unaffected mother into induced pluripotent stem cells (iPSCs) and differentiated the iPSCs into induced neural crest cells (iNCCs), the key cell type required for correct craniofacial development. BMKS patient-derived iPSCs proliferated more slowly than both mother- and unrelated control-derived iPSCs, and RNA-Seq analysis revealed significant differences in gene expression and alternative splicing. Patient iPSCs displayed defective differentiation into iNCCs compared to maternal and unrelated control iPSCs, in particular a delay in undergoing an epithelial-to-mesenchymal transition (EMT). RNA-Seq analysis of differentiated iNCCs revealed widespread gene expression changes and mis-splicing in genes relevant to craniofacial and embryonic development that highlight a dampened response to WNT signalling, the key pathway activated during iNCC differentiation. Furthermore, we identified the mis-splicing of TCF7L2 exon 4, a key gene in the WNT pathway, as a potential cause of the downregulated WNT response in patient cells. Additionally, mis-spliced genes shared common sequence properties such as length, branch point to 3' splice site (BPS-3'SS) distance and splice site strengths, suggesting that splicing of particular subsets of genes is particularly sensitive to changes in TXNL4A expression. Together, these data provide the first insight into how reduced TXNL4A expression in BMKS patients might compromise splicing and NCC function, resulting in defective craniofacial development in the embryo.


Assuntos
Processamento Alternativo , Atresia das Cóanas/patologia , Surdez/congênito , Regulação da Expressão Gênica no Desenvolvimento , Cardiopatias Congênitas/patologia , Células-Tronco Pluripotentes Induzidas/citologia , Modelos Biológicos , Ribonucleoproteína Nuclear Pequena U5/deficiência , Spliceossomos/fisiologia , Apoptose , Diferenciação Celular , Técnicas de Reprogramação Celular , Atresia das Cóanas/genética , Células Clonais , Surdez/genética , Surdez/patologia , Transição Epitelial-Mesenquimal , Éxons/genética , Face/embriologia , Facies , Feminino , Cabeça/embriologia , Cardiopatias Congênitas/genética , Humanos , Crista Neural/citologia , Regiões Promotoras Genéticas/genética , Sítios de Splice de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ribonucleoproteína Nuclear Pequena U5/genética , Deleção de Sequência , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Via de Sinalização Wnt
3.
PLoS One ; 15(5): e0232900, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32413090

RESUMO

Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and also by merle on chromosome 10. Pigment-associated deafness is also seen in other species, including cats, mice, sheep, alpacas, horses, cows, pigs, and humans, but the genetic factors determining why some piebald or merle dogs develop deafness while others do not have yet to be determined. Here we perform a genome-wide association study (GWAS) to identify regions of the canine genome significantly associated with deafness in three dog breeds carrying piebald: Dalmatian, Australian cattle dog, and English setter. We include bilaterally deaf, unilaterally deaf, and matched control dogs from the same litter, phenotyped using the brainstem auditory evoked response (BAER) hearing test. Principal component analysis showed that we have different distributions of cases and controls in genetically distinct Dalmatian populations, therefore GWAS was performed separately for North American and UK samples. We identified one genome-wide significant association and 14 suggestive (chromosome-wide) associations using the GWAS design of bilaterally deaf vs. control Australian cattle dogs. However, these associations were not located on the same chromosome as the piebald locus, indicating the complexity of the genetics underlying this disease in the domestic dog. Because of this apparent complex genetic architecture, larger sample sizes may be needed to detect the genetic loci modulating risk in piebald dogs.


Assuntos
Surdez/veterinária , Doenças do Cão/genética , Animais , Estudos de Casos e Controles , Surdez/congênito , Surdez/genética , Cães , Potenciais Evocados Auditivos , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Testes Auditivos , Polimorfismo de Nucleotídeo Único , Seleção Artificial , Pigmentação da Pele/genética
4.
Nucleic Acids Res ; 48(9): 5065-5080, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32249312

RESUMO

Disabling hearing loss impacts ∼466 million individuals worldwide with 34 million children affected. Gene and pharmacotherapeutic strategies to rescue auditory function in mouse models of human deafness are most effective when administered before hearing onset, after which therapeutic efficacy is significantly diminished or lost. We hypothesize that preemptive correction of a mutation in the fetal inner ear prior to maturation of the sensory epithelium will optimally restore sensory function. We previously demonstrated that transuterine microinjection of a splice-switching antisense oligonucleotide (ASO) into the amniotic cavity immediately surrounding the embryo on embryonic day 13-13.5 (E13-13.5) corrected pre-mRNA splicing in the juvenile Usher syndrome type 1c (Ush1c) mouse mutant. Here, we show that this strategy only marginally rescues hearing and partially rescues vestibular function. To improve therapeutic outcomes, we microinjected ASO directly into the E12.5 inner ear. A single intra-otic dose of ASO corrects harmonin RNA splicing, restores harmonin protein expression in sensory hair cell bundles, prevents hair cell loss, improves hearing sensitivity, and ameliorates vestibular dysfunction. Improvements in auditory and vestibular function were sustained well into adulthood. Our results demonstrate that an ASO pharmacotherapeutic administered to a developing organ system in utero preemptively corrects pre-mRNA splicing to abrogate the disease phenotype.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas do Citoesqueleto/genética , Surdez/congênito , Surdez/tratamento farmacológico , Oligonucleotídeos Antissenso/uso terapêutico , Vestíbulo do Labirinto/fisiopatologia , Âmnio , Animais , Limiar Auditivo/efeitos dos fármacos , Proteínas de Ciclo Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , Surdez/genética , Surdez/fisiopatologia , Orelha Interna/efeitos dos fármacos , Orelha Interna/metabolismo , Feto , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/ultraestrutura , Camundongos , Microinjeções , Mutação , Oligonucleotídeos Antissenso/administração & dosagem , Splicing de RNA/efeitos dos fármacos , Vestíbulo do Labirinto/efeitos dos fármacos
5.
PLoS Genet ; 16(4): e1008643, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32294086

RESUMO

Hereditary hearing loss is challenging to diagnose because of the heterogeneity of the causative genes. Further, some genes involved in hereditary hearing loss have yet to be identified. Using whole-exome analysis of three families with congenital, severe-to-profound hearing loss, we identified a missense variant of SLC12A2 in five affected members of one family showing a dominant inheritance mode, along with de novo splice-site and missense variants of SLC12A2 in two sporadic cases, as promising candidates associated with hearing loss. Furthermore, we detected another de novo missense variant of SLC12A2 in a sporadic case. SLC12A2 encodes Na+, K+, 2Cl- cotransporter (NKCC) 1 and plays critical roles in the homeostasis of K+-enriched endolymph. Slc12a2-deficient mice have congenital, profound deafness; however, no human variant of SLC12A2 has been reported as associated with hearing loss. All identified SLC12A2 variants mapped to exon 21 or its 3'-splice site. In vitro analysis indicated that the splice-site variant generates an exon 21-skipped SLC12A2 mRNA transcript expressed at much lower levels than the exon 21-included transcript in the cochlea, suggesting a tissue-specific role for the exon 21-encoded region in the carboy-terminal domain. In vitro functional analysis demonstrated that Cl- influx was significantly decreased in all SLC12A2 variants studied. Immunohistochemistry revealed that SLC12A2 is located on the plasma membrane of several types of cells in the cochlea, including the strial marginal cells, which are critical for endolymph homeostasis. Overall, this study suggests that variants affecting exon 21 of the SLC12A2 transcript are responsible for hereditary hearing loss in humans.


Assuntos
Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/genética , Mutação , Domínios Proteicos/genética , Membro 2 da Família 12 de Carreador de Soluto/química , Membro 2 da Família 12 de Carreador de Soluto/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Cloretos/metabolismo , Cóclea/metabolismo , Cóclea/patologia , Surdez/congênito , Surdez/genética , Éxons/genética , Feminino , Expressão Gênica , Células HEK293 , Humanos , Lactente , Macaca fascicularis , Masculino , Linhagem , Splicing de RNA , RNA Mensageiro/análise , RNA Mensageiro/genética , Membro 2 da Família 12 de Carreador de Soluto/metabolismo
6.
Harefuah ; 159(1): 117-122, 2020 Feb.
Artigo em Hebraico | MEDLINE | ID: mdl-32048492

RESUMO

INTRODUCTION: Deafness is the most common sensory disability in humans affecting all aspects of life. Approximately 50% of congenital deafness is hereditary and about half of genetic deafness is still unsolved. To date, more than 150 genes are known to cause hearing loss worldwide, with specific genes contributing to deafness in distinct populations. Of these, more than 20 genes are involved in deafness among the Jewish Israeli hearing-impaired population. The most common gene in many worldwide populations, including Israel, is GJB2, which encodes the connexin 26 protein. The second most common gene among Jews is TMC1, with most pathogenic variants found only among Jews of Moroccan origin. Most other pathogenic variants found in the Jewish population are origin-specific and not found in other Jewish ethnic groups or in other worldwide populations. In patients where hereditary deafness is suspected, known variants in the specific ethnicity are routinely examined. In Israel, the GJB2 gene is screened in all cases of hereditary deafness and the TMC1 gene is screened in deaf persons of Jewish Moroccan origin. In cases where no variant is found in a known gene, more comprehensive diagnostic tests should be used. Since the beginning of the deep sequencing era, less than a decade ago, the number of deafness-related genes in the Jewish population has increased by threefold. Identifying the pathogenic variant makes it possible to study molecular pathogenesis, to anticipate and understand the prognosis, to calculate probability of concomitant morbidity, to offer prenatal diagnosis, prevent recurrence of deafness in the family and early rehabilitation. Currently, cochlear implant offers the greatest chance for rehabilitation. The hope is that understanding the molecular pathogenesis will in the future lead to personalized medical treatment. We review the genetics of deafness, with an emphasis on the Jewish population in Israel, new diagnostic methods and suggest a diagnostic algorithm and future treatment methods.


Assuntos
Surdez/congênito , Conexina 26 , Humanos , Israel , Judeus , Mutação
7.
Indian J Ophthalmol ; 68(1): 250-253, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31856543

RESUMO

A 47-year-old lady (index case) with diabetes and deafness showed multiple oval circumferential areas of perifoveal atrophy in both eyes. Autofluorescence revealed areas of hypoautofluorescence. Optical coherence tomography (OCT) showed depression of inner retinal surface, inner retinal hyporeflective spaces (pseudocysts), disorganization/thinning of outer retina, outer retinal tubulation, loss of external limiting membrane, ellipsoid and interdigitation zone, and thinning of the retinal pigment epithelium and choriocapillaris. The patient was evaluated using OCT angiogram. Retinal lesions of her mother (68-year-old) were very obvious on autofluorescence imaging. The result of A3243G mutation in MTTL1 gene was positive in the index case confirming the diagnosis of maternally inherited diabetes and deafness (MIDD).


Assuntos
Cistos/diagnóstico , Surdez/congênito , Diabetes Mellitus/congênito , Angiofluoresceinografia/métodos , Retina/patologia , Doenças Retinianas/etiologia , Tomografia de Coerência Óptica/métodos , Cistos/etiologia , Surdez/genética , Diabetes Mellitus/genética , Feminino , Humanos , Herança Materna , Pessoa de Meia-Idade , Doenças Retinianas/diagnóstico
8.
Laryngoscope ; 130(3): 776-781, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31087657

RESUMO

OBJECTIVE: The U.S. Food and Drug Administration guidelines for cochlear implantation (CI) include age greater than 12 months. Studies have suggested that implantation in children younger than 12 months with congenital deafness may be associated with better spoken language outcomes. Compare auditory comprehension (AC) outcomes for children with congenital deafness who received CI less than 12 months of age to those implanted at 12 to 24 months of age. METHODS: Retrospective review of prospectively collected data in consecutively implanted patients under 2 years of age who received CI and had post-CI Preschool Language Scale (PLS)-AC scores. Receptive language was assessed with the AC subtest of the PLS. Patients without pre-CI PLS-AC scores were excluded. The association between age at implantation and post-CI PLS-AC scores up to 2 years after CI surgery was modeled using a linear mixed-effects model. Time from CI surgery, number of implants, risk factors for language delay, pre-CI PLS-AC score, and sex were included in the model. Patients implanted less than 12 months of age were compared to those implanted between 12 and 24 months. RESULTS: Twenty-nine patients who had CI surgery by 12 months and 82 who had CI surgery between 12 and 24 months were included in the analysis. Younger age at implantation and better pre-CI PLS-AC scores were significantly associated with better post-CI PLS-AC scores. CONCLUSION: Cochlear implantation in children with congenital deafness less than 12 months of age was associated with better PLS-AC than in children implanted over 12 months of age up to 2 years after implantation. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:776-781, 2020.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez/congênito , Surdez/cirurgia , Audição , Fatores Etários , Pré-Escolar , Implante Coclear/normas , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do Tratamento
9.
J Int Adv Otol ; 15(3): 352-357, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31846911

RESUMO

OBJECTIVES: Jervell and Lange-Nielsen syndrome is a rare autosomal recessive disease characterized by congenital sensorineural deafness and significant QT interval prolongation. Aims were to study the prevalence of long QT in congenital hearing loss, complications encountered, outcomes by Categories of auditory Performance (CAP) scores and Speech Intelligibility Rating (SIR) scores and to create an algorithm with precautions to be followed in Long QT children. MATERIALS AND METHODS: Study was done at Auditory implant center at a tertiary referral care ENT hospital which includes 41 paediatric patients who were diagnosed to have Long QT during preoperative assessment and underwent cochlear implantation. A standard Protocol was followed in all candidates which includes comprehensive targeted history and investigations, preoperative and intraoperative precautions, and the findings were recorded. RESULTS: Preoperative prophylactic Beta blockers, avoiding sympathetic stimulation and drugs prolonging QT interval with rational use of Magnesium Sulphate and standby of defibrillator were the standard precautions practised. Fatal Arrhythmias were encountered intra-operatively in five patients which was treated with cardiac pacing. Cardiac monitoring was done intraoperatively and during switch-on. Significant improvement in CAP and SIR scores were observed at 3 and 6 months when compared to their base line values. CONCLUSION: With special attention to preoperative evaluation, appropriate intraoperative precautions and monitoring, judicious surgical planning and post surgical follow-up cochlear implantation may be performed safely in patients with JLNS with good postoperative results allowing for improved audition.


Assuntos
Implante Coclear/métodos , Surdez/cirurgia , Perda Auditiva Neurossensorial/cirurgia , Síndrome de Jervell-Lange Nielsen/cirurgia , Percepção Auditiva , Pré-Escolar , Surdez/congênito , Surdez/fisiopatologia , Feminino , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/fisiopatologia , Humanos , Síndrome de Jervell-Lange Nielsen/complicações , Síndrome de Jervell-Lange Nielsen/fisiopatologia , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Inteligibilidade da Fala , Resultado do Tratamento
10.
J Int Adv Otol ; 15(3): 364-367, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31846912

RESUMO

OBJECTIVES: The aim of the present study was to analyze the outcomes of cochlear implantation (CI) in patients with agenesis of the corpus callosum (CCA). A literature review and a retrospective analysis of our cochlear implant database were performed. MATERIALS AND METHODS: To the best of our knowledge, in the English literature, there was only one case reported with CCA who had undergone CI surgery. This case had Donnai-Barrow syndrome. In the Cukurova University School of Medicine Department of Otorhinolaryngology database, 5 of the 1317 patients who underwent CI surgery who had CCA were selected. The patients' demographic characteristics, operative findings, surgical outcomes, and additional disabilities were investigated. The patients' preoperative and postoperative Listening Progress Profile (LiP) and Meaningful Auditory Integration Scale (MAIS) tests were done to analyze the auditory performances. RESULTS: The participants of the study were 5 (0.38%) individuals (2 male and 3 female patients; ages 5.5, 7.5, 8, 9, and 12 years). Two of the patients had total agenesis, and the other three had partial agenesis of the CCA. In the histories of the patients, one patient had parental consanguinity, and one had febrile convulsion. No patient had an additional disability. None had experienced device failure. No patients were non-users or limited users of cochlear implants. Postoperative LiP and MAIS test scores were improved for all patients nearly as the patients without any deformity. They showed normal auditory performance in the analysis in their postoperative 48 months of follow-up. CONCLUSION: Patients who had CCA are good candidates for CI surgery.


Assuntos
Agenesia do Corpo Caloso/cirurgia , Implante Coclear , Surdez/cirurgia , Agenesia do Corpo Caloso/complicações , Criança , Pré-Escolar , Surdez/congênito , Feminino , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/cirurgia , Testes Auditivos , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Desenvolvimento da Linguagem , Masculino , Miopia/congênito , Miopia/cirurgia , Proteinúria/congênito , Proteinúria/cirurgia , Erros Inatos do Transporte Tubular Renal/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Proc Natl Acad Sci U S A ; 116(51): 25948-25957, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31776257

RESUMO

The function of outer hair cells (OHCs), the mechanical actuators of the cochlea, involves the anchoring of their tallest stereocilia in the tectorial membrane (TM), an acellular structure overlying the sensory epithelium. Otogelin and otogelin-like are TM proteins related to secreted epithelial mucins. Defects in either cause the DFNB18B and DFNB84B genetic forms of deafness, respectively, both characterized by congenital mild-to-moderate hearing impairment. We show here that mutant mice lacking otogelin or otogelin-like have a marked OHC dysfunction, with almost no acoustic distortion products despite the persistence of some mechanoelectrical transduction. In both mutants, these cells lack the horizontal top connectors, which are fibrous links joining adjacent stereocilia, and the TM-attachment crowns coupling the tallest stereocilia to the TM. These defects are consistent with the previously unrecognized presence of otogelin and otogelin-like in the OHC hair bundle. The defective hair bundle cohesiveness and the absence of stereociliary imprints in the TM observed in these mice have also been observed in mutant mice lacking stereocilin, a model of the DFNB16 genetic form of deafness, also characterized by congenital mild-to-moderate hearing impairment. We show that the localizations of stereocilin, otogelin, and otogelin-like in the hair bundle are interdependent, indicating that these proteins interact to form the horizontal top connectors and the TM-attachment crowns. We therefore suggest that these 2 OHC-specific structures have shared mechanical properties mediating reaction forces to sound-induced shearing motion and contributing to the coordinated displacement of stereocilia.


Assuntos
Células Ciliadas Auditivas Externas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Estereocílios/metabolismo , Membrana Tectorial/metabolismo , Animais , Cóclea/citologia , Surdez/congênito , Surdez/genética , Surdez/metabolismo , Predisposição Genética para Doença , Células Ciliadas Auditivas Externas/citologia , Células Ciliadas Vestibulares/metabolismo , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/genética , Camundongos , Camundongos Knockout , Membrana Tectorial/citologia
12.
Acta Otolaryngol ; 139(12): 1090-1097, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31671009

RESUMO

Background: There are some debates regarding the benefit from cochlear implantation (CI) for prelingually deaf children with white matter changes.Objective: To assess the hearing and speech outcomes of prelingually deaf children with white matter changes (group A), and those with complete deafness (group B), at 2 years after CI.Material and Methods: Study 1 included 32 and 34 children in group A and B, respectively. The Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR) were used to assess the performance on hearing and speech. Study 2 included eight children with white matter changes and eight with complete deafness at 2 years post-CI, and nine normal-hearing peers. The mismatch response (MMR) to the stimulus pair 'ba'/'pa' was investigated.Results: There was no significant difference on CAP or SIR scores between the children in group A and B. All children with white matter changes showed MMRs to Mandarin consonants at 2 years post-CI. And there was no significant difference on the incidence, the latency or amplitude of MMR among three groups.Conclusions and significance: Most prelingually deaf children with white matter changes got good outcomes from CI. CI is not a contraindication for most individuals with white matter changes.


Assuntos
Implante Coclear/reabilitação , Surdez/cirurgia , Leucoencefalopatias/complicações , Audiometria da Fala , Criança , Pré-Escolar , Implante Coclear/psicologia , Surdez/complicações , Surdez/congênito , Surdez/reabilitação , Potenciais Evocados , Feminino , Seguimentos , Humanos , Lactente , Masculino , Inteligibilidade da Fala
14.
Acta Otolaryngol ; 139(11): 990-997, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31550964

RESUMO

Background: Few studies on speech performance of children after cochlear implantation (CI) described isolated large vestibular aqueduct syndrome (LVAS). Objective: To investigate speech developmental trajectories of infants with LVAS after CI, and to compare with those who have structurally normal inner ears. Materials and methods: 1112 infants with congenital severe to profound hearing loss participated in this study. 150 infants in group A were diagnosed with LVAS, 962 infants in group B with structurally normal inner ear. The speech performance was assessed via the Meaningful Use of Speech Scale (MUSS). The evaluations were performed pre-implant, 1, 3, 6, 9, 12, 24, 36, 48 and 60 months after CI. Results: The mean scores of the MUSS improved over a 5-year period after implantation in both groups A and B. The LVAS group presented similar speech developmental trajectory to the non-LVAS group at each assessment interval, except pre-operation. There were significant differences in mean scores between vocalizing behavior and oral communication skills, clarification skills of infants in both two groups. Conclusions and significance: Speech performance of infants with LVAS developed rapidly after CI and was similar to infants with structurally normal inner ear. For infants with isolated LVAS, CI had a significant effect and should be recommended as a therapeutic option.


Assuntos
Implante Coclear , Surdez/congênito , Desenvolvimento da Linguagem , Pré-Escolar , Surdez/cirurgia , Feminino , Humanos , Lactente , Masculino , Inteligibilidade da Fala , Aqueduto Vestibular
15.
Int J Pediatr Otorhinolaryngol ; 126: 109630, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31442870

RESUMO

OBJECTIVES: More than 50% of congenital hearing loss is attributed to genetic factors. Data of gene mutation associated with hearing loss from large population studies in Chinese population are scarce. In this study, we conducted a comprehensive newborn genetic screening in China to establish the carrier frequency and mutation spectrum of deafness-associated genes. METHODS: A total of 53,033 newborns were screened for hearing defects associated mutations. Twenty hot spot mutations in GJB2, GJB3, SLC26A4 and mitochondria12S rRNA were examined using suspension array analysis. RESULTS: 14,185 newborns (26.75%) were identified with at least one mutated allele. 872 (1.64%) neonates carried homozygous mutations including 112 (0.21%) mitochondrial DNA homoplasmy, 228 (0.43%) were compound heterozygotes, and 11,985 (22.59%) were heterozygotes including 11 (0.02%) mitochondrial DNA heteroplasmy. Top five mutations included 109 G > A, 235 delC, 299-300 delAT in GJB2, IVS7-2 A > G in SLC26A4 and 1555 A > G in mitochondria12S rRNA. Notably, a total of 10,995 neonates (20.73%) carried 109 G > A in GJB2. Moreover, the allele frequencies of 109 G > A were detected 11.61% in Guangdong, 10.44% in Sichuan and 2.88% in Shandong, respectively, a significant difference in prevalence among these geographic regions (p<0.01). In addition, the high frequency of 109 G > A in GJB2 was confirmed by a TaqMan probe-based qPCR assay. Very recently, the ClinGen Hearing Loss Expert Panel reached a consensus and confirmed its pathogenic role in hearing impairment. CONCLUSION: We delineated the mutation profile of common deafness-causing genes in the Chinese population and highlighted the high prevalence of 109 G > A pathogenic mutation. Our study may facilitate early diagnosis/intervention and genetic counseling for hearing impairment in clinical practice.


Assuntos
Conexinas/genética , Surdez/genética , Testes Genéticos , Mutação , Triagem Neonatal , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Grupo com Ancestrais do Continente Asiático/genética , China/epidemiologia , Surdez/congênito , Surdez/epidemiologia , Feminino , Frequência do Gene , Heterozigoto , Homozigoto , Humanos , Recém-Nascido , Masculino , Mitocôndrias/genética , Prevalência , RNA Ribossômico/genética , Transportadores de Sulfato/genética
16.
Int J Pediatr Otorhinolaryngol ; 126: 109625, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31442872

RESUMO

OBJECTIVES: A cochlear implant (CI) has the potential to improve the functioning of a deaf child in many aspects. Nevertheless, the dynamics of the general development, beyond the typically measured language abilities, directly after CI, is still unknown, especially if a child is implanted early. In this study we present a methodological framework for assessment of different domains of development, as well as the central auditory nervous system (CANS) maturation in infants and toddlers with a CI. METHODS: Three children with bilateral congenital hearing loss and a unilateral CI, aged below 2.5 years, participated in a longitudinal study. Children were tested at three time points after cochlear implantation using the Polish Children Development Scale (CDS) consisting of a comprehensive battery of tests, as well as recordings of Cortical Auditory Evoked Potentials (CAEP). RESULTS: All three children revealed gradual improvement in the overall CDS result as well as most of the CDS subscales. After 9 months of CI experience two younger children showed age-appropriate performance. In CAEP measurements a decrease of latency of the P1 component (an established biomarker of cortical auditory maturation) was observed in the same two children, with one achieving normal ranges of P1 latency after 9 months of CI use. CONCLUSIONS: Our novel methodological framework can be successfully applied in small children with cochlear implants. It contributes to better understanding of the general development in early implanted children. The preliminary results indicate variability in children's performance in various developmental domains and thus the need to monitor the development of each child individually and holistically.


Assuntos
Desenvolvimento Infantil , Implantes Cocleares , Surdez/cirurgia , Potenciais Evocados Auditivos , Criança , Pré-Escolar , Cognição , Surdez/congênito , Feminino , Humanos , Desenvolvimento da Linguagem , Estudos Longitudinais , Masculino
17.
Genes (Basel) ; 10(7)2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31336982

RESUMO

Labyrinthine aplasia, microtia, and microdontia (LAMM) is an autosomal recessive condition causing profound congenital deafness, complete absence of inner ear structures (usually Michel's aplasia), microtia (usually type 1) and microdontia. To date, several families have been described with this condition and a number of mutations has been reported. We report on eight further cases of LAMM syndrome including three novel mutations, c. 173T>C p.L58P; c. 284G>A p.(Arg95Gln) and c.325_327delinsA p.(Glu109Thrfs*18). Congenital deafness was the primary presenting feature in all affected individuals and consanguinity in all but two families. We compare the features in our patients to those previously reported in LAMM, and describe a milder, asymmetrical phenotype associated with FGF3 mutations.


Assuntos
Microtia Congênita/genética , Microtia Congênita/patologia , Orelha Interna/anormalidades , Fator 3 de Crescimento de Fibroblastos/genética , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/patologia , Anormalidades Dentárias/genética , Anormalidades Dentárias/patologia , Adulto , Pré-Escolar , Consanguinidade , Análise Mutacional de DNA , Surdez/congênito , Orelha Interna/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Fenótipo
18.
Acta Otolaryngol ; 139(6): 479-486, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035849

RESUMO

BACKGROUND: Usher syndrome (USH) is an autosomal recessive disease characterized by hearing loss, vision loss, and occasionally vestibular dysfunction. Klinefelter syndrome (KS) is an X chromosome polyploidy characterized by one or more additional X chromosomes in males. To date, there has been no report of USH combined with KS. OBJECTIVES: This study examined the causative genes in three Chinese probands with congenital hearing loss. MATERIAL AND METHODS: Targeted next-generation sequencing (NGS) was performed to identify mutations in three probands with hearing loss. Low-coverage whole-genome sequencing (WGS) analysis of aneuploidy was used to verify the chromosome aneuploidy. RESULTS: Four novel MYO7A mutations were identified in two USH1 probands who were initially diagnosed with nonsyndromic hearing loss until the onset of vision loss. Another case was initially diagnosed with nonsyndromic hearing loss and USH2 and KS were discovered incidentally after the genetic analysis. CONCLUSIONS: Our findings expand the mutation spectrum of MYO7A. This is also the first report of concomitant USH and KS. Genetic testing can help with clinical management, particularly if an unrecognized syndromic disorder is identified before the onset of additional symptoms. A clinical genetic evaluation is recommended as part of the diagnostic work-up in congenital hearing loss.


Assuntos
Surdez/genética , Predisposição Genética para Doença , Testes Genéticos/métodos , Síndrome de Klinefelter/genética , Miosina VIIa/genética , Síndromes de Usher/genética , Criança , China , Implantes Cocleares , Surdez/congênito , Feminino , Auxiliares de Audição , Humanos , Síndrome de Klinefelter/diagnóstico , Masculino , Multimorbidade , Mutação , Prognóstico , Amostragem , Síndromes de Usher/diagnóstico
19.
Am J Audiol ; 28(1): 62-68, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30938557

RESUMO

Purpose The aim of the current study was to review all pediatric cases with congenital deafness who underwent bilateral implantation in our center. Specifically, auditory performance and speech intelligibility ratings were compared across children based on their mode of bilateral stimulation (simultaneous or sequential implantation). Method A retrospective chart review design was used in this study. A total of 46 congenitally deaf children were included. Children ranged in age between 2 and 8 years, with a mean of 3 years 7 months. Participants were divided into 2 groups: those who received their bilateral implant simultaneously and those who received them sequentially. Categories of Auditory Performance (CAP; Archbold, Lutman, & Marshall, 1995 ) scores and Speech Intelligibility Rating (SIR; M. C. Allen, Nikolopoulos, & O'Donoghue, 1998 ) scores were used to measure their performance. Results Children scored an average of 4.1 (±1.6) on the CAP Scale and 1.6 (±1) on the SIR Scale. Results showed that children who received their implants simultaneously scored relatively higher on the CAP Scale than those with sequential implants. However, there were no differences between the 2 groups in SIR scores. These 2 outcome measures were not correlated with age at implantation. Conclusion The current study demonstrated that simultaneous implantation could potentially improve audiologic outcome.


Assuntos
Implante Coclear/métodos , Surdez/reabilitação , Inteligibilidade da Fala , Percepção Auditiva , Criança , Pré-Escolar , Surdez/congênito , Surdez/fisiopatologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Percepção da Fala , Inquéritos e Questionários , Resultado do Tratamento
20.
Am J Hum Genet ; 104(5): 914-924, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30982611

RESUMO

Glypicans are a family of cell-surface heparan sulfate proteoglycans that regulate growth-factor signaling during development and are thought to play a role in the regulation of morphogenesis. Whole-exome sequencing of the Australian family that defined Keipert syndrome (nasodigitoacoustic syndrome) identified a hemizygous truncating variant in the gene encoding glypican 4 (GPC4). This variant, located in the final exon of GPC4, results in premature termination of the protein 51 amino acid residues prior to the stop codon, and in concomitant loss of functionally important N-linked glycosylation (Asn514) and glycosylphosphatidylinositol (GPI) anchor (Ser529) sites. We subsequently identified seven affected males from five additional kindreds with novel and predicted pathogenic variants in GPC4. Segregation analysis and X-inactivation studies in carrier females provided supportive evidence that the GPC4 variants caused the condition. Furthermore, functional studies of recombinant protein suggested that the truncated proteins p.Gln506∗ and p.Glu496∗ were less stable than the wild type. Clinical features of Keipert syndrome included a prominent forehead, a flat midface, hypertelorism, a broad nose, downturned corners of mouth, and digital abnormalities, whereas cognitive impairment and deafness were variable features. Studies of Gpc4 knockout mice showed evidence of the two primary features of Keipert syndrome: craniofacial abnormalities and digital abnormalities. Phylogenetic analysis demonstrated that GPC4 is most closely related to GPC6, which is associated with a bone dysplasia that has a phenotypic overlap with Keipert syndrome. Overall, we have shown that pathogenic variants in GPC4 cause a loss of function that results in Keipert syndrome, making GPC4 the third human glypican to be linked to a genetic syndrome.


Assuntos
Surdez/congênito , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/patologia , Variação Genética , Glipicanas/genética , Deformidades Congênitas das Extremidades Inferiores/genética , Deformidades Congênitas das Extremidades Inferiores/patologia , Adulto , Criança , Pré-Escolar , Surdez/genética , Surdez/patologia , Feminino , Humanos , Lactente , Masculino , Linhagem , Fenótipo , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...