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Atopic dermatitis is a chronic complex inflammatory skin disorder that requires sustainable treatment methods due to the limited efficacy of conventional therapies. Sargassum serratifolium, an algal species with diverse bioactive substances, is investigated in this study for its potential benefits as a therapeutic agent for atopic dermatitis. RNA sequencing of LPS-stimulated macrophages treated with ethanolic extract of Sargassum serratifolium (ESS) revealed its ability to inhibit a broad range of inflammation-related signaling, which was proven in RAW 264.7 and HaCaT cells. In DNCB-induced BALB/c or HR-1 mice, ESS treatment improved symptoms of atopic dermatitis within the skin, along with histological improvements such as reduced epidermal thickness and infiltration of mast cells. ESS showed a tendency to improve serum IgE levels and inflammation-related cytokine changes, while also improving the mRNA expression levels of Chi3l3, Ccr1, and Fcεr1a genes in the skin. Additionally, ESS compounds (sargachromanol (SCM), sargaquinoic acid (SQA), and sargahydroquinoic acid (SHQA)) mitigated inflammatory responses in LPS-treated RAW264.7 macrophages. In summary, ESS has an anti-inflammatory effect and improves atopic dermatitis, ESS may be applied as a therapeutics for atopic dermatitis.
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Dermatite Atópica , Dinitroclorobenzeno , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C , Sargassum , Animais , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/patologia , Sargassum/química , Camundongos , Células RAW 264.7 , Humanos , Etanol/química , Extratos Vegetais/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Imunoglobulina E/sangue , Citocinas/metabolismoRESUMO
BACKGROUND: Dystonia is a heterogeneous movement disorder involving various genetic backgrounds, and the implication of whole exome sequencing (WES) has yet to be clearly elucidated. In this study, we performed WES in Korean patients with young-onset dystonia. METHODS: We recruited patients with young-onset dystonia based on the new MDS dystonia classification at Samsung Medical Centre from 2015 to 2019. We excluded subjects diagnosed by single gene tests (GCH1, TOR1A, PANK2, PRRT2, and SGCE) or levodopa trials and subjects with focal or possible secondary dystonia. We performed WES in all enrolled subjects and confirmed the results with Sanger sequencing. RESULTS: Of the 43 patients, we detected 11 disease-causing variants, classified as either pathogenic or likely pathogenic, in 9 patients (20.9%). Generalized dystonia, infancy-childhood-onset dystonia, and other combined neurologic manifestations were related with PV/LPV. When we retrospectively reviewed the patients with PV/LPV, brain imaging was diagnostic in 3 subjects (HTRA1, SCL20A, and WDR45), clinical characteristics of paroxysmal presentation were observed in 2 (ADCY5 and ATP1A3), and microcephaly was noted in 1 patient (KMT2B). CONCLUSION: Clinical exome sequencing is helpful for the diagnosis of dystonia, especially for that with infancy-childhood onset, and generalized dystonia with other neurologic manifestations. Additionally, careful evaluations and examinations could provide information for selecting candidates for genetic testing.
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Distonia , Distúrbios Distônicos , Humanos , Criança , Distonia/diagnóstico , Distonia/genética , Sequenciamento do Exoma , Estudos Retrospectivos , Distúrbios Distônicos/diagnóstico , Distúrbios Distônicos/genética , Testes Genéticos , Mutação/genética , Chaperonas Moleculares/genética , ATPase Trocadora de Sódio-Potássio/genética , Proteínas de Transporte/genéticaRESUMO
BACKGROUND: The human skin-derived precursors (SKPs) are a good cell source for regeneration. However, the isolation of SKP from human skin is limited. To overcome this drawback, we hypothesized that the component of plant stem cells could convert human fibroblasts to SKPs. METHODS: Human dermal fibroblasts were treated with shikimic acid, a major component of Sequoiadendron giganteum callus extract. The characteristics of these reprogrammed cells were analyzed by qPCR, western blot, colony-forming assay, and immunofluorescence staining. Artificial human skin was used for CO2 laser-induced wound experiments. Human tissues were analyzed by immunohistochemistry. RESULTS: The reprogrammed cells expressed nestin (a neural precursor-specific protein), fibronectin, and vimentin and could differentiate into the ectodermal and mesodermal lineage. Nestin expression was induced by shikimic acid through the mannose receptor and subsequent MYD88 activation, leading to P38 phosphorylation and then CREB binding to the nestin gene promoter. Finally, we confirmed that shikimic acid facilitated the healing of cut injury and enhanced dermal reconstruction in a human artificial skin model. Moreover, in a clinical study with healthy volunteers, plant callus extracts increased the expression of stem cell markers in the basal layer of the epidermis and collagen deposit in the dermis. CONCLUSIONS: These results indicate that shikimic acid is an effective agent for tissue regeneration.
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Células-Tronco Multipotentes , Ácido Chiquímico , Diferenciação Celular , Células Cultivadas , Fibroblastos , Humanos , PeleAssuntos
Anastomose em-Y de Roux , Colangiopancreatografia Retrógrada Endoscópica , Enteroscopia de Duplo Balão , Ducto Hepático Comum/cirurgia , Jejuno/cirurgia , Idoso , Anastomose em-Y de Roux/efeitos adversos , Anastomose Cirúrgica , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Colangiopancreatografia Retrógrada Endoscópica/métodos , Constrição Patológica/etiologia , Enteroscopia de Duplo Balão/efeitos adversos , Enteroscopia de Duplo Balão/instrumentação , Enteroscopia de Duplo Balão/métodos , Feminino , Humanos , RecidivaAssuntos
Deficiência Intelectual/diagnóstico , Imageamento por Ressonância Magnética , Espasticidade Muscular/diagnóstico , Atrofia Óptica/diagnóstico , Paraplegia Espástica Hereditária/diagnóstico , Ataxias Espinocerebelares/diagnóstico , Avaliação de Sintomas/métodos , Adulto , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Ilustração MédicaRESUMO
Genes that are primarily expressed in cochlear glia-like supporting cells (GLSs) have not been clearly associated with progressive deafness. Herein, we present a deafness locus mapped to chromosome 3p25.1 and an auditory neuropathy spectrum disorder (ANSD) gene, TMEM43, mainly expressed in GLSs. We identify p.(Arg372Ter) of TMEM43 by linkage analysis and exome sequencing in two large Asian families segregating ANSD, which is characterized by inability to discriminate speech despite preserved sensitivity to sound. The knock-in mouse with the p.(Arg372Ter) variant recapitulates a progressive hearing loss with histological abnormalities in GLSs. Mechanistically, TMEM43 interacts with the Connexin26 and Connexin30 gap junction channels, disrupting the passive conductance current in GLSs in a dominant-negative fashion when the p.(Arg372Ter) variant is introduced. Based on these mechanistic insights, cochlear implant was performed on three subjects, and speech discrimination was successfully restored. Our study highlights a pathological role of cochlear GLSs by identifying a deafness gene and its causal relationship with ANSD.
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Códon sem Sentido , Conexinas/metabolismo , Genes Dominantes , Perda Auditiva Central/genética , Proteínas de Membrana/genética , Animais , Implante Coclear , Feminino , Perda Auditiva Central/metabolismo , Perda Auditiva Central/fisiopatologia , Perda Auditiva Central/cirurgia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Linhagem , Percepção da FalaRESUMO
INTRODUCTION: Besides cerebellar ataxia, various other movement disorders, including dystonia, could manifest as main clinical symptoms in ataxia-telangiectasia (A-T). However, the clinical characteristics of dystonic A-T patients are not clearly elucidated. METHODS: To investigate the characteristics of dystonic A-T, we screened previous reports with A-T patients presenting dystonia as a main manifestation, and included 38 dystonic A-T patients from 16 previous studies and our 2 cases. We reviewed clinical and demographic data of dystonic A-T patients. Additionally, to figure out clinical meaning of cerebellar involvement in dystonic A-T, we divided them into two groups based on the presence of cerebellar involvement, and compared clinical features between two groups. RESULTS: In the patients with dystonic A-T, dystonia tended to appear during childhood or adolescence and became generalized over time. Choreoathetosis and myoclonus accompanied more frequently than the typical clinical features, including cerebellar ataxia or atrophy, telangiectasia, or oculomotor apraxia. Additionally, alpha-fetoprotein level was also elevated in the patients with dystonic A-T. When we compared dystonic A-T with and without cerebellar involvement, the former was related with more chance for telangiectasia and oculomotor apraxia, while the latter with that for choreoathetosis and malignancy. CONCLUSION: Even without ataxia, telangiectasia, or oculomotor apraxia, A-T should be considered in undiagnosed dystonia, especially generalized dystonia which started from childhood or adolescence period, and alpha-fetoprotein level can be a useful screening tool. In addition, cerebellar involvement is important considering different phenotype in dystonic A-T patients with and without cerebellar sign.
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Ataxia Telangiectasia/diagnóstico , Ataxia Telangiectasia/genética , Distonia/diagnóstico , Distonia/genética , Adolescente , Ataxia Telangiectasia/fisiopatologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Distonia/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
BACKGROUND: Hereditary cerebellar ataxias exhibit heterogeneous phenotypes and genotypes. To date, advancement of next-generation sequencing technologies have identified many causative genes for ataxia in various population. In this study, whole-exome sequencing (WES) was utilized to explore the genetic cause of ataxia among Korean patients who remained undiagnosed following routine investigation. METHODS: Patients with ataxia were enrolled in this study. We excluded patients with acquired, degenerative, and trinucleotide repeat ataxias, such as spinocerebellar ataxia 1 (SCA1), SCA2, SCA3, SCA6, SCA7, SCA8, SCA17, Dentatorubral-pallidoluysian atrophy, and Friedreich ataxia. WES was performed. After basic filtering based on population databases, we then performed primary filtering to screen for known ataxia-associated genes, followed by expanded filtering customized for individual patients. RESULTS: We enrolled 77 ataxia patients from 68 families. Eighteen families had pathogenic or likely pathogenic variants in 14 different genes, including NEU1, APTX, SPG7, HTRA1, POLG2, SYNE1, CACNA1G, CACNA1A, ITPR1, AHI1, SPG11, ANO10, ATM, and C5orf42, resulting in a diagnostic yield of 26.5%. Hereditary spastic paraplegia was the most common diagnosis. Adult-onset ataxias and those without family history were frequently encountered. Variants of unknown significance were found in 14 (20.6%) families, some of which were highly probable from the clinical perspective. CONCLUSION: Using WES, we explored the molecular etiology of ataxia in patients whom were not diagnosed through routine clinical investigation. This study revealed unexpected rare disorders as well as the known ataxia-associated genes in a Korean population.
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Ataxia/genética , Ataxia Cerebelar/genética , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , República da Coreia , Sequenciamento do Exoma , Adulto JovemRESUMO
Although the KMT2B gene was identified as a causative gene for early-onset generalized dystonia, the efficacy of deep brain stimulation (DBS) in KMT2B-related dystonia has not been clearly elucidated. Here, we describe a 28-year-old woman who developed generalized dystonia with developmental delay, microcephaly, short stature, and cognitive decline. She was diagnosed with KMT2B- related dystonia using whole-exome sequencing with a heterozygous frameshift insertion of c.515dupC (p.T172fs) in the KMT2B gene. Oral medications and botulinum toxin injection were not effective. The dystonia markedly improved with bilateral pallidal DBS (the Burke-Fahn-Marsden Dystonia Rating Scale score was reduced from 30 to 5 on the dystonia movement scale and from 11 to 1 on the disability scale), and she could walk independently. From this case, we suggest that bilateral globus pallidus internus DBS can be an effective treatment option for patients with KMT2B-related generalized dystonia.
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CHARGE syndrome has a clinically broad spectrum of phenotypes, including partial or atypical type. CHD7 mutation is related to CHARGE syndrome that shows various phenotypes according to the CHD7 variant. Developments in genetic analysis techniques, such as next-generation sequencing (NGS), are helping both diagnosis and treatment of diseases. We report the case of a preterm infant diagnosed with atypical CHARGE who has a novel and de novo CHD7 variant that was identified using whole-genome sequencing (WGS). Neonatologists tend to be reluctant to diagnose infants with multiple malformations because they have to focus on treating life-threatening complications; however, NGS is considered helpful for the early diagnosis of broad-spectrum anomalies during the neonatal period.
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Síndrome CHARGE , Síndrome CHARGE/diagnóstico , Síndrome CHARGE/genética , DNA Helicases/genética , Proteínas de Ligação a DNA/genética , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , MutaçãoRESUMO
DNA polymerase δ, whose catalytic subunit is encoded by POLD1, is responsible for synthesizing the lagging strand of DNA. Single heterozygous POLD1 mutations in domains with polymerase and exonuclease activities have been reported to cause syndromic deafness as a part of multisystem metabolic disorder or predisposition to cancer. However, the phenotypes of diverse combinations of POLD1 genotypes have not been elucidated in humans. We found that five members of a multiplex family segregating autosomal recessive nonsyndromic sensorineural hearing loss (NS-SNHL) have revealed novel compound heterozygous POLD1 variants (p.Gly1100Arg and a presumptive null function variant, p.Ser197Hisfs*54). The recombinant p.Gly1100Arg polymerase δ showed a reduced polymerase activity by 30-40%, but exhibited normal exonuclease activity. The polymerase activity in cell extracts from the affected subject carrying the two POLD1 mutant alleles was about 33% of normal controls. We suggest that significantly decreased polymerase δ activity, but not a complete absence, with normal exonuclease activity could lead to NS-SNHL.
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DNA Polimerase III/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Perda Auditiva/diagnóstico , Perda Auditiva/genética , Adulto , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Biomarcadores , DNA Polimerase III/metabolismo , Ativação Enzimática , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Masculino , Mutação , Linhagem , Fenótipo , Polimorfismo de Nucleotídeo Único , Irmãos , Síndrome , Sequenciamento do ExomaRESUMO
Background: Youth suicides have diverse characteristics according to the young people's developmental stages. Warning signs and communication of suicidal intent can be vague among early adolescents, while mental health problems may be more evidently related to suicidal ideation in older adolescents. Understanding the developmental characteristics of youth suicide is necessary for effective suicide prevention. Aims: We explored the differences between children and adolescents who died by suicide and the characteristics of these young people as observed by their school teachers. Method: We analyzed teachers' mandatory postmortem reports of suicides among 308 Korean students. We compared: suicide-related information including personal, familial, and school factors; stressful life events; and participation in interventions among elementary, middle, and high school students who died by suicide. We also assessed the distribution of student suicides per month. Results: Suicide among elementary school students increased during school vacations, and suicide among middle and high school students increased during the school semester. According to the teachers' reports, elementary school students who died by suicide were more extroverted and had better academic achievements than their high school peers, and had significantly lower levels of substance/tobacco use. Elementary school students who died by suicide showed significantly less academic stress and use of external professional help than did other groups. Limitations: Because this research is based on mandatory teacher reports, the subjective opinions of teachers may have affected the reliability of the data. Suicide by out-of-school youth was not included. Conclusion: School-based suicide prevention should be implemented in accordance with young people's developmental characteristics.
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Sucesso Acadêmico , Conflito Familiar , Estresse Psicológico , Suicídio Consumado , Adolescente , Criança , Depressão , Status Econômico , Características da Família , Feminino , Amigos , Humanos , Comportamento Impulsivo , Masculino , Personalidade , República da Coreia , Serviços de Saúde Mental Escolar , Estações do AnoRESUMO
Microcephaly is a prevalent phenotype in patients with neurodevelopmental problems, often with genetic causes. We comprehensively investigated the clinical phenotypes and genetic background of microcephaly in 40 Korean patients. We analyzed their clinical phenotypes and radiologic images and conducted whole exome sequencing (WES) and analysis of copy number variation (CNV). Infantile hypotonia and developmental delay were present in all patients. Thirty-four patients (85%) showed primary microcephaly. The diagnostic yield from the WES and CNV analyses was 47.5%. With WES, we detected pathogenic or likely pathogenic variants that were previously associated with microcephaly in 12 patients (30%); nine of these were de novo variants with autosomal dominant inheritance. Two unrelated patients had mutations in the KMT2A gene. In 10 other patients, we found mutations in the GNB1, GNAO1, TCF4, ASXL1, SMC1A, VPS13B, ACTG1, EP300, and KMT2D genes. Seven patients (17.5%) were diagnosed with pathogenic CNVs. Korean patients with microcephaly show a genetic spectrum that is different from that of patients with microcephaly of other ethnicities. WES along with CNV analysis represents an effective approach for diagnosis of the underlying causes of microcephaly.
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A copper-catalyzed three-component annulation for the synthesis of functionalized 2-quinolones was developed. Three reactions including an SN2, a Knoevenagel, and finally C-N bond formation are involved in the designed cascade reaction using 2-bromoacylarenes, 2-iodoacetamide, and nucleophiles as the three components. A new catalytic system was discovered during the study and this modular approach is highly efficient to access functionalized 2-quinolone derivatives, compatible with a broad range of functional groups, scalable, and step-economic. Further derivatization of the obtained product demonstrates the synthetic utility of this method.
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BACKGROUND: Diaphanous-related formin 1 (DIA1), which assembles the unbranched actin microfilament and microtubule cytoskeleton, is encoded by DIAPH1. Constitutive activation by the disruption of autoinhibitory interactions between the N-terminal diaphanous inhibitory domain (DID) and C-terminal diaphanous autoregulatory domain (DAD) dysregulates DIA1, resulting in both hearing loss and blood cell abnormalities. METHODS AND RESULTS: Here, we report the first constitutively active mutant in the DID (p.A265S) of humans with only hearing loss and not blood cell abnormality through whole exome sequencing. The previously reported DAD mutants and our DID mutant (p.A265S) shared the finding of diminished autoinhibitory interaction, abnormally upregulated actin polymerisation activity and increased localisations at the plasma membrane. However, the obvious defect in the DIA1-driven assembly of cytoskeleton 'during cell division' was only from the DAD mutants, not from p.A265S, which did not show any blood cell abnormality. We also evaluated the five DID mutants in the hydrophobic pocket since four of these five additional mutants were predicted to critically disrupt interaction between the DID and DAD. These additional pathogenic DID mutants revealed varying degrees of defect in the DIA1-driven cytoskeleton assembly, including nearly normal phenotype during cell division as well as obvious impaired autoinhibition, again coinciding with our key observation in DIA1 mutant (p.A265S) in the DID. CONCLUSION: Here, we report the first mutant in the DID of humans with only hearing loss. The differential cell biological phenotypes of DIA1 during cell division appear to be potential determinants of the clinical severity of DIAPH1-related cytoskeletopathy in humans.
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Divisão Celular/genética , Citoesqueleto/genética , Forminas/genética , Perda Auditiva/genética , Citoesqueleto de Actina/genética , Citoesqueleto/patologia , Feminino , Estudos de Associação Genética , Perda Auditiva/patologia , Humanos , Masculino , Microtúbulos/genética , Proteínas Mutantes/genética , Mutação/genética , Domínios Proteicos/genética , Sequenciamento do ExomaRESUMO
OBJECTIVE: The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the GNAL mutation. METHODS: We provide the first report of a dystonia patient with a genetically confirmed GNAL mutation in the Korean population and reviewed the literature on patients with the GNAL mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the GNAL mutation compared to that in patients with DYT1 and DYT6 in a previous study. RESULTS: Patients with the GNAL mutation and those with DYT1 had higher early responder rates (GNAL, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (p = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (p = 0.278). The decrease in the dystonia motor scale score in the GNAL group was 46.9% at early follow-up and 63.4% at late follow-up. CONCLUSION: GPi-DBS would be an effective treatment option for dystonia patients with the GNAL mutation who are resistant to medication or botulinum toxin treatment.
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BACKGROUND: We investigated the characteristics of adolescents who committed suicide in South Korea, and how these characteristics differed by gender. METHOD: Data from middle and high school students who committed suicide between 2014 and 2016 were analyzed. We evaluated differences in suicide method and place, personal characteristics, and school life characteristics by gender using the Chi square test and t test. RESULTS: Jumping from a high place was the most common suicide method for both male and female students. A significantly greater proportion of female adolescents had experienced depressive symptoms, previous self-injury, previous suicide attempts, and had problems with school attendance and peers. Additionally, they were more likely to be classified as high risk according to a school-based mental health screening test and to utilize professional mental health treatment services. CONCLUSION: Our results demonstrate that adolescents who committed suicide exhibited gender differences in personal characteristics and school life. These characteristics might aid in the development of adolescent suicide policies and intervention programs.
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Otoancorin (OTOA), encoded by OTOA, is required for the development of the tectorial membrane in the inner ear. Mutations in this gene cause nonsyndromic hearing loss (DFNB22). The molecular mechanisms underlying most DFNB22 remain poorly understood. Disruption of glycosylphosphatidylinositol (GPI) anchorage has been assumed to be the pathophysiology mandating experimental validation. From a Korean deaf family, we identified two trans OTOA variants (c.1320 + 5 G > C and p.Gln589ArgfsX55 [NM_144672.3]) . The pathogenic potential of c.1320 + 5 G > C was confirmed by a minigene splicing assay. To experimentally determine the GPI anchorage, wild-type (WT) and mutant OTOA harboring p.Gln589ArgfsX55 were expressed in HEK293T cells. The mutant OTOA with p.Gln589ArgfsX55 resulted in an uncontrolled release of OTOA into the medium in contrast with phosphatidylinositol-specific phospholipase C-induced controlled release of WT OTOA from the cell surface. Together, the results of this reverse translational study confirmed GPI-anchorage of OTOA and showed that downstream sequences from the 589th amino acid are critical for GPI-anchorage.
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Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Variação Genética , Glicosilfosfatidilinositóis/metabolismo , Perda Auditiva/genética , Perda Auditiva/metabolismo , Alelos , Processamento Alternativo , Biomarcadores , Predisposição Genética para Doença , Genótipo , Perda Auditiva/diagnóstico , HumanosRESUMO
The mutational spectrum of deafness in Indochina Peninsula, including Vietnam, remains mostly undetermined. This significantly hampers the progress toward establishing an effective genetic screening method and early customized rehabilitation modalities for hearing loss. In this study, we evaluated the genetic profile of severe-to-profound hearing loss in a Vietnamese pediatric population using a hierarchical genetic analysis protocol that screened 11 known deafness-causing variants, followed by massively parallel sequencing targeting 129 deafness-associated genes. Eighty-seven children with isolated severe-to-profound non-syndromic hearing loss without family history were included. The overall molecular diagnostic yield was estimated to be 31.7%. The mutational spectrum for severe-to-profound non-syndromic hearing loss in our Vietnamese population was unique: The most prevalent variants resided in the MYO15A gene (7.2%), followed by GJB2 (6.9%), MYO7A (5.5%), SLC26A4 (4.6%), TMC1 (1.8%), ESPN (1.8%), POU3F4 (1.8%), MYH14 (1.8%), EYA1 (1.8%), and MR-RNR1 (1.1%). The unique spectrum of causative genes in the Vietnamese deaf population was similar to that in the southern Chinese deaf population. It is our hope that the mutation spectrum provided here could aid in establishing an efficient protocol for genetic analysis of severe-to-profound hearing loss and a customized screening kit for the Vietnamese population.