RESUMO
OBJECTIVE: This study was conducted to investigate the hypothesis that patients using ß-blockers will develop hearing loss. DESIGN: A cross-sectional study. STUDY SAMPLE: A total of 125 patients completed the study. A total of 63 patients were on ß-blockers and 62 were not on ß-blockers. RESULTS: Carvedilol was significantly associated with hearing loss. Other beta-blockers including metoprolol and atenolol showed no association with hearing loss. Linear multiple regression analysis was run including variables of gender, age, ischaemic heart disease, cardiac failure/dilated cardiomyopathy, frusemide and carvedilol use as predictors for total hearing loss severity at all frequencies. Age and gender, as well as carvedilol, were found to be the only statistically significant predictors for hearing loss severity. CONCLUSION: Chronic use of carvedilol was associated with significant hearing loss. This may need to be taken into account when prescribing the drug. Further randomised controlled studies with baseline audiometric hearing tests before starting treatment, and periodic follow-up tests, would provide a better assessment of the effect of carvedilol on hearing.
Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Carvedilol/efeitos adversos , Perda Auditiva/induzido quimicamente , Audição/efeitos dos fármacos , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Feminino , Perda Auditiva/diagnóstico , Perda Auditiva/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Adulto JovemRESUMO
Donnai-Barrow syndrome (DBS; MIM 222448) is characterized by typical craniofacial anomalies (major hypertelorism with bulging eyes), high grade myopia, deafness and low molecular weight proteinuria. The disorder results from mutations in the low density lipoprotein receptor-related protein 2 gene LRP2 that maps to chromosome 2q31.1. LRP2 encodes megalin, a multi-ligand endocytic receptor. Herein, we describe the clinical presentation of 4 patients from 2 unrelated Saudi families. Two novel LRP2 mutations, a homozygous nonsense mutation (c.4968C>G; p.Tyr1656*) and a missense mutation (c.12062G>A; p.Cys4021Tyr), were detected in the first and second family respectively. Interestingly, intrafamilial phenotypic variability was observed in one family, while DBS features were atypical in the second family. Differential diagnosis of DBS includes several syndromes associating hypertelorism with high grade myopia, and several syndromal forms of CDH, which are briefly summarized in this study.
Assuntos
Agenesia do Corpo Caloso/genética , Perda Auditiva Neurossensorial/genética , Hérnias Diafragmáticas Congênitas/genética , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Miopia/genética , Proteinúria/genética , Erros Inatos do Transporte Tubular Renal/genética , Adolescente , Agenesia do Corpo Caloso/metabolismo , Criança , Pré-Escolar , Códon sem Sentido , Análise Mutacional de DNA , Feminino , Expressão Gênica , Perda Auditiva Neurossensorial/metabolismo , Hérnias Diafragmáticas Congênitas/metabolismo , Humanos , Lactente , Recém-Nascido , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Mutação de Sentido Incorreto , Miopia/metabolismo , Proteinúria/metabolismo , Erros Inatos do Transporte Tubular Renal/metabolismo , Adulto JovemRESUMO
Hearing loss is one of the most common sensory disorders in humans and has a genetic cause in 50% of the cases. Our recent studies indicate that nonsyndromic hearing loss (NSHL) in the Saudi Arabian population is genetically heterogeneous and is not caused by mutations in GJB2 and GJB6, the most common genes for deafness in various populations worldwide. Identification of the causative gene/mutation in affected families is difficult due to extreme genetic heterogeneity and lack of phenotypic variability. We utilized an SNP array-based whole-genome homozygosity mapping approach in search of the causative gene, for the phenotype in a consanguineous Saudi family, with five affected individuals presenting severe to profound congenital NSHL. A single shared block of homozygosity was identified on chromosome 19p13.3 encompassing GIPC3, a recently identified hearing loss gene. Subsequently, a novel mutation c.122 C>A (p.T41K) in GIPC3 was found. This is the first report of GIPC3 mutation in a Saudi family. The presence of the GIPC3 mutations in only one of 100 Saudi families with congenital NSHL suggests that it appears to be a rare cause of familial or sporadic deafness in this population.