RESUMEN
Background: Approximately 70% of congenital deafness is attributable to genetic causes. Incidence of congenital deafness is known to be higher in families with consanguineous marriage. In this study, we investigated the genetic causes in three consanguineous Pakistani families segregating with prelingual, severe-to-profound deafness. Results: Through targeted next-generation sequencing of 414 genes known to be associated with deafness, homozygous variants c.536del (p. Leu180Serfs∗20) in TECTA, c.3719 G>A (p. Arg1240Gln) in MYO7A, and c.482+1986_1988del in HGF were identified as the pathogenic causes of enrolled families. Interestingly, in one large consanguineous family, an additional c.706G>A (p. Glu236Lys) variant in the X-linked POU3F4 gene was also identified in multiple affected family members causing deafness. Genotype-phenotype cosegregation was confirmed in all participating family members by Sanger sequencing. Conclusions: Our results showed that the genetic causes of deafness are highly heterogeneous. Even within a single family, the affected members with apparently indistinguishable clinical phenotypes may have different pathogenic variants.
Asunto(s)
Sordera/genética , Proteínas de la Matriz Extracelular/genética , Factor de Crecimiento de Hepatocito/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Miosina VIIa/genética , Factores del Dominio POU/genética , Adulto , Anciano , Consanguinidad , Femenino , Proteínas Ligadas a GPI/genética , Genes Ligados a X/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Pakistán , Linaje , FenotipoRESUMEN
OBJECTIVE: It remains elusive which factors may influence the morbidity and mortality of lung metastasis (LM) in Laryngeal Squamous Cell Carcinoma (LSCC) patients. The aim of the present study was to investigate factors influencing LM and the survival outcomes of LSCC patients with LM. METHODS: We identified 10,935 patients with LSCC from 2010 to 2014 using the Surveillance, Epidemiology and End Results database. Multivariate logistic regression analysis was used to determine the factors associated with the presence of LM. Multivariate cox regression analysis was used to identify covariates associated with increased all-cause mortality in patients with LM. RESULTS: Among 10,935 patients with LSCC, 232 (2.12%) patients had LM. The median survival time of patients with LM was 8 months, and 8.37% of patients survived after 3 years. Patients with age ≥ 60 years old, unmarried status, supraglottis, overlapping lesion of larynx, subglottis, pathological grade III, T4 stage, N1 stage, N2 stage, N3 stage and bone, brain or liver metastases were more likely to have LM. Survival analysis showed that chemotherapy and radiotherapy suggested better survival of LSCC patients with LM while pathological grade IV was associated with an increased all-cause mortality. CONCLUSION: The incidence of LSCC patients with LM varied by age, married status, and tumor subtypes. LSCC patients with LM had poor survival, and only 8.37% of patients survived after 3 years. However, chemotherapy and radiotherapy were found as independent favorable prognostic factors for survival.
Asunto(s)
Carcinoma de Células Escamosas/secundario , Neoplasias Laríngeas/patología , Neoplasias Pulmonares/secundario , Distribución por Edad , Anciano , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , China/epidemiología , Femenino , Humanos , Incidencia , Neoplasias Laríngeas/mortalidad , Modelos Logísticos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Estado Civil , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Programa de VERF , Análisis de SupervivenciaRESUMEN
The mechanism of nasopharyngeal carcinoma (NPC) remains unclear. The present study investigated the abnormal expression of long non-coding (lnc)RNAs in NPC tissues and one NPC cell line to identify the involvement of lncRNAs in the tumorigenesis of NPC. Using a quantitative reverse transcription polymerase chain reaction (RT-qPCR), the expression of lncRNA C22orf32-1 in NPC tissues and an NPC cell line was verified. The effects of lncRNA C22orf32-1 on NPC cells were investigated with a cell proliferation assay, cell scratch assay, Transwell assay and a cell apoptosis assay. The expression levels of lncRNA C22orf32-1 in NPC tissues and an NPC cell line were upregulated. lncRNA C22orf32-1 promoted the proliferation, migration and invasion of NPC cells, and reduced the apoptosis of NPC cells. The data demonstrated that lncRNA C22orf32-1 may facilitate the tumorigenesis of NPC, and may be used for the early diagnosis and treatment of NPC.