Caroça, Cristina; Campelo, Paula; Caria, Helena; Paço, João; Silva, Susana
Background: São Tomé and Príncipe (STP) is a least developed country (LDC) on Sub-Saharan Africa, in which was
detected a high prevalence of sensorineural Hearing Loss (SNHL). HL is a common condition with both genetic and
environmental causes, and it greatly impacts on global health. STP population has leading with additional health
problems over the years, such as anaemia and malaria infection. The present study aims to identify the correlation
between the most prevalent G6PD variants and the high prevalence of HL in STP population. Methods: A sample
of 316 individuals collected during Humanitarian Missions in STP, was retrospectively studied in a case-control
approach to evaluate...
Chora, J.; Simões-Teixeira, H.; Matos, T. D.; Martins, J. H.; Alves, M.; Ferreira, R.; Silva, L.; Ribeiro, C.; Fialho, G.; Caria, H.
Gonçalves, A. C.; Chora, J.; Matos, T. D.; O'Neill, A.; Escada, P.; Fialho, G.; Caria, H.
Caroça, Cristina; Vicente, Vera; Campelo, Paula; Chasqueira, Maria; Caria, Helena; Silva, Susana; Paixão, Paulo; Paço, João
Background: Rubella infection can affect several organs and cause birth defects that are responsible for congenital
rubella syndrome (CRS). Congenital hearing loss is the most common symptom of this syndrome, occurring in
approximately 60% of CRS cases. Worldwide, over 100 000 babies are born with CRS every year. There is no specific
treatment for rubella, but the disease is preventable by vaccination. Since 1969, the rubella vaccine has been
implemented in many countries, but in Africa, only a few countries routinely immunize against rubella. The aim of
this study was to estimate the rate of infection from the wild-type rubella virus in São Tomé and...
Haider, H. F.; Hoare, D. J.; Costa, R. F.; Potgieter, Iskra; Kikidis, D.; Lapira, A.; Nikitas, C.; Caria, H.; Cunha, N.; Paço, J.
Matos, T. D.; Simões-Teixeira, H.; Caria, Helena; Gonçalves, A. C.; Chora, J.; Correia, M. C.; Moura, C.; Rosa, H.; Monteiro, L.; O'Neill, A.; Dias, O.; Andrea, M.; Fialho, G.
Objective: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese
nonsyndromic sensorineural hearing loss (NSSHL) patients. Design: Sequencing of the coding region,
basal promoter, exon 1 and donor splice site of the GJB2 gene; screening for the presence of the two
common GJB6 deletions. Study sample: A cohort of 264 Portuguese NSSHL patients. Results: At least
one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two
mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least
one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only...
Caria, Helena; Matos, T. D.; Oliveira-Soares, R.; Santos, A. R.; Galhardo, I.; Soares-Almeida, L.; Dias, Ó.; Andrea, M.; Correia, C.; Fialho, G.
Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible for familial
nonepidermolytic palmoplantar keratoderma (NEPPK) associated with deafness without any additional
features. To date, only a few cases have been described. We report a Portuguese pedigree presenting an inherited
combination of NEPPK and sensorineural deafness compatible with maternal transmission. Clinical
expression and age of onset of NEPPK and deafness were variable. Normal expression patterns of epidermal
keratins and filaggrin, intercellular junction proteins including connexin 26, loricrin and cornified envelope
proteins, were observed. Molecular analysis revealed that all the affected members, previously screened for
Cx26 mutations with negative results, presented the mtDNA A7445G point mutation...
Simões-Teixeira, Helena; Matos, Tiago D.; Marques, Marta Canas; Dias, Óscar; Andrea, Mário; Barreiros, Eduardo; Barreiros, Luís; Moreno, Felipe; Fialho, Graça; Caria, Helena; Castillo, Ignacio del
Matos, T. D.; Simões-Teixeira, H.; Caria, Helena; Cascão, R.; Rosa, H.; O'Neill, A.; Dias, O.; Andrea, M.E.; Kelsell, D. P.; Fialho, G.
Involvement of GJB2 noncoding regions in hearing loss (HL) has not been extensively investigated. However, three noncoding
mutations, c.-259C>T, c.-23G>T, and c.-23+1G>A, were reported. Also, c.-684 -675del, of uncertain pathogenicity, was found
upstream of the basal promoter. We performed a detailed analysis of GJB2 noncoding regions in Portuguese HL patients
(previously screened for GJB2 coding mutations and the common GJB6 deletions) and in control subjects, by sequencing the basal
promoter and flanking upstream region, exon 1, and 3’UTR. All individuals were genotyped for c.-684 -675del and 14 SNPs. Novel
variants (c.-731C>T, c.-26G>T, c.∗45G>A, and c.∗985A>T) were found in controls. A hearing individual homozygous for c.-684...
Hilgert, Nele; Caria, Helena; Van Camp, Guy
Hereditary hearing loss (HL) is a very heterogeneous trait, with 46 gene identifications for non-syndromic HL. Mutations in GJB2 cause up to half of all cases of severe-to-profound congenital autosomal recessive non-syndromic HL, with 35delG being the most frequent mutation in Caucasians. Although a genotype-phenotype correlation has been established for most GJB2 genotypes, the HL of 35delG homozygous patients is mild to profound. We hypothesise that this phenotypic variability is at least partly caused by the influence of modifier genes. By performing a whole-genome association (WGA) study on 35delG homozygotes, we sought to identify modifier genes. The association study was...