Faculdade de Ciências

Individual’s hearing performance after cochlear implant (CI) is variable and depends on different factors such as etiology of deafness, age at implantation, and social/family hearing environment. Here we report the case of dizygotic twins, boy and girl, presenting with neurosensorial profound deafness prior CI (age of implantation = 3.5 years old). Both parents have severe/profound deafness, since childhood, and use sign language as primary mode of communication. Clinical and genetic characterization was performed, as well as the assessment of the auditory and oral (re)habilitation after CI, applying a battery of audiological, speech, and language tests. The twin girl and the father were homozygous for the c.35delG mutation in the GJB2 gene, while the twin boy and the mother were compound heterozygotes, both monoallelic for c.35delG and for the deletion del(GJB6-D13S1830) in theGJB6gene. The remaining hearing impaired relatives were c.35delG homozygotes. The genetic cause of deafnes...

Presbycusis or age-related hearing loss (ARHL) is the most common sensory impairment in older adults. It affects millions of people worldwide, leading to social isolation and exclusion of valid citizens. ARHL is characterized by bilateral progressive hearing loss predominant in the high frequencies. It is a multifactorial condition with etiologic factors both environmental and genetic, the latter dictating an intrinsic susceptibility to presbycusis. Previous candidate gene studies in different populations found an association between presbycusis and genes involved in hereditary deafness or in oxidative metabolism. Mitochondrial haplogroups U and K in an Australian population, and the NAT2*6A haplotype in Europe, were found to be significantly associated with ARHL. In addition, three different GWAS have recently been published and a highly significant and replicated SNP in GRM7 gene was identified. We have audiologically assessed a meaningful sample of Portuguese elder individuals an...

The DFNB1 locus (GJB2 and GJB6 genes) is a major cause of nonsyndromic sensorineural hearing loss (NSSHL), being responsible for over 1/5 of the Portuguese cases. However, some patients present only one recessive mutation. The frequency of such individuals is, in several instances, higher than the expected if they were only carriers. This fact suggests the existence of an accompanying DFNB1 mutation in some cases. We have noticed a conserved region in the GJB2 intron, which might be a potential location of pathogenic mutations. We have thus investigated that conserved region in 27 NSSHL Portuguese patients (previously analysed regarding the basal promoter, exon 1, donor splice site, coding region and 3’UTR) harbouring one pathogenic, controversial or unclear GJB2 mutation, and none of the two common GJB6 deletions (del1830 and del1854). The control sample consisted in 42 normal-hearing individuals from the general population. The 69 subjects were analysed by direct sequencing. A tot...

To anyone acquainted with the genetics of deafness, GJB2 is the most familiar and well known gene, in which novel mutations are still being found. From the beginning it became clear that some GJB2 mutations are more prevalent in certain world regions or ethnicities and nowadays, with more than 200 different mutations, polymorphisms and novel variants described, population specificity is even more evident. Thus, when faced with probands requiring GJB2 diagnosis or genetic counseling, it is very helpful to have full knowledge of mutation prevalence in their region of origin. Previous studies concerning deafness genetics in Portugal, and focusing on GJB2, have suggested that mutation spectrum of this gene in our population it’s not exactly like other Mediterranean or western European countries. Portuguese history may explain part of this specificity. In this study we set out to extend the investigation on GJB2 mutation prevalence in the general population by screening about 900 random ...

Abstract Introduction Hearing loss is the most common sensory disability and is present in about 1.9 per 1000 infants at birth. The DFNB1 locus (13q11-q12) includes the genes GJB2, coding for connexin 26, and GJB6, encoding connexin 30. More than 100 mutations have been identified associated with autosomal dominant and recessive hearing loss in the GJB2 gene. Objectives The aim of the present study was to identify the genetic aetiology of deafness in two Portuguese individuals, presenting nonsyndromic sensorineural moderate and severe hearing loss, respectively. Patients and methods The individuals were evaluated in both ears by pure tone audiometry and blood samples were collected after written informed consent was signed. DNA extraction and PCR amplification of GJB2 coding region followed standard methodologies. PCR products were automatically sequenced in both directions. Results We identified a novel mutation, c.638T>A (p.Leu213X), in GJB2 gene. This nonsense mutation was fou...

Objective: A high heterogeneity of GJB2 variants has been observed around the world in different populations. Moreover, the prevalence of some variants was shown to be population specific. Therefore, in order to facilitate molecular diagnosis of congenital deafness and improve genetic counselling in each country/region, it is important to determine the prevalence of the different GJB2 alleles among the population. In this study, aiming at determining the spectrum and prevalence of GJB2 variants in the Portuguese population, we extended our previous studies on the carrier frequency of GJB2 mutations by screening neonates, born in different Portuguese regions and randomly selected from the general population. Methods: We have analysed a total of about 470 samples of neonates representing the major regions of Portugal mainland. Screening of GJB2 gene was performed by direct sequencing of the entire coding region. Results and Discussion: The analysis of the 470 samples included in the p...

Introduction: Presbycusis or age-related hearing loss (ARHL) is one of the major chronic diseases affecting the elderly population, and may become a major health problem if considering the increase in life expectancy. ARHL is characterized by progressive, bilateral high-frequency hearing loss starting in the third decade, predominately in the high frequencies and affecting the speech spectrum frequencies within the fifth decade. It results from degeneration of cochlear structures within the inner ear. Many studies on presbycusis have been developed in different populations. Mitochondrial haplogroups U and K in an Australian population, and the NAT2*6A haplotype in Europe, were found to be significantly associated with ARHL. The 4977bp mtDNA deletion was also shown to be associated with the process of aging and with ARHL. Objectives: In this study we analyzed a sample of the elderly Portuguese population with presbycusis (n=100) for (i) SNPs on the NAT2 gene, (ii) the presence of the...

OBJECTIVE: A high heterogeneity of GJB2 variants has been observed around the world in different populations. Moreover, the prevalence of some variants was shown to be populations’ specific. Therefore, in order to facilitate molecular diagnosis of congenital deafness and improve genetic counseling in each country/region, it is important to determine the prevalence of the different GJB2 alleles among the population In this study, aiming at idenfying regional differences, we extended our previous studies on the carrier frequency of GJB2 mutations by screening random neonates from different Portuguese regions. METHODS: We have considered a total of about 230 samples of neonates representing the major regions of Portugal mainland. Screening of GJB2 gene was performed by sequencing the entire coding region. RESULTS: The analysis of the 230 samples included in this study led to the identification of different carriers of common GJB2 mutations and polymorphisms, some of them found for the ...

Introduction. Hearing loss is a condition that interferes with the development of the child at a cognitive and language level. Therefore, early diagnosis of deafness is important for earlier (re)habilitation, namely through the use of cochlear implants. GJB2 mutation testing is now routinely performed for etiologic studies of deafness, and some previous reports suggest that children with GJB2-related deafness are good cochlear implant (CI) candidates. Preliminary studies on a sample of Portuguese individuals with CI show that nearly half of the individuals tested have mutations in GJB2, being 35delG the most common mutant allele, as expected. The data on (re)habilitation success of patients with GJB2-related deafness indicate that they have a good oral performance, thus confirming that they are good CI candidates. However, no significant differences were found in the oral rehabilitation success between both groups – GJB2 positive or negative Objectives. The aim of the present study ...

Hearing impairment affects approximately 1 in 1000 newborns and at least 60% of these cases have a genetic origin. Despite large genetic heterogeneity, mutations in a single gene - GJB2 - are the most frequent genetic cause of severe to profound pre-lingual recessive deafness in many populations. Therefore, GJB2 became the most important gene in the understanding of deafness. Hearing loss is a condition that interferes with the development of the child at a cognitive and language level. Therefore early diagnosis of deafness is important for earlier rehabilitation, namely through the use of cochlear implants. These devices replace the cochlea in a physiological context. Some studies suggest a correlation between the GJB2 genotype of the implanted individual and a phenotype that allows the success of rehabilitation due to cochlear implant The aim of our study is to analyse the GJB2 gene in a sample of 100 Portuguese cochlear implant recipients. All individuals, presenting non-syndromi...