Publicação
Investigation of the genetic etiology of sensorineural hearing loss in portuguese patients
| Resumo: | About 2/1000 new born present hearing loss (HL) and of these, approximately 50% can be genetically explained. In this work, 70 Portuguese probands presenting nonsyndromic sensorineural HL were investigated for the presence of mutations in the DFNB1 locus. Mutation c.35delG, in the GJB2 gene, was first screened by restriction analysis. Two individuals were homozygous (2,9%) and five (7,1%) heterozygous for this mutation. The GJB2 coding exon was then analysed by sequencing in cases found to be negative or heterozygous for the c.35delG mutation. A novel mutation, p.Leu213X, was identified. This mutation wasn’t present in a random control sample of 480 individuals from the Portuguese population previously sequenced. Along with the two c.35delG homozygous, the genetic cause for HL due to GJB2 mutations could be determined for six more individuals, representing a total of 11,4% of the probands. The most frequent GJB6 deletions were further screened by multiplex PCR in individuals negative or monoallelic for GJB2 mutations. No mutation was found. Three common mitochondrial DNA mutations associated to HL were investigated by enzymatic restriction in 143 families, previously screened for DFNB1 and compatible with maternal inheritance. Only the m.1555A>G mutation was found, in one of the analysed families. Two cases of low-frequency sensorineural HL were investigated regarding the most relevant exons of WFS1 gene. A novel mutation, p.Asp171Asn, was found in exon 5 of WFS1 gene. This mutation wasn’t present in 100 Portuguese hearing controls later sequenced. Two cases of Pendred Syndrome were studied. No mutation was found in the relevant exons analysed. So, the genetic cause couldn´t yet be determined. This study represents a contribution for extending the knowledge on hereditary HL in the Portuguese population, either in the identification of the genetic etiology in affected families, or in the development of more accurate diagnostic protocols. |
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| Autores principais: | Gonçalves, Ana Cláudia Gasparinho, 1989- |
| Assunto: | Biologia molecular Surdez Mutações Teses de mestrado - 2012 |
| Ano: | 2012 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | About 2/1000 new born present hearing loss (HL) and of these, approximately 50% can be genetically explained. In this work, 70 Portuguese probands presenting nonsyndromic sensorineural HL were investigated for the presence of mutations in the DFNB1 locus. Mutation c.35delG, in the GJB2 gene, was first screened by restriction analysis. Two individuals were homozygous (2,9%) and five (7,1%) heterozygous for this mutation. The GJB2 coding exon was then analysed by sequencing in cases found to be negative or heterozygous for the c.35delG mutation. A novel mutation, p.Leu213X, was identified. This mutation wasn’t present in a random control sample of 480 individuals from the Portuguese population previously sequenced. Along with the two c.35delG homozygous, the genetic cause for HL due to GJB2 mutations could be determined for six more individuals, representing a total of 11,4% of the probands. The most frequent GJB6 deletions were further screened by multiplex PCR in individuals negative or monoallelic for GJB2 mutations. No mutation was found. Three common mitochondrial DNA mutations associated to HL were investigated by enzymatic restriction in 143 families, previously screened for DFNB1 and compatible with maternal inheritance. Only the m.1555A>G mutation was found, in one of the analysed families. Two cases of low-frequency sensorineural HL were investigated regarding the most relevant exons of WFS1 gene. A novel mutation, p.Asp171Asn, was found in exon 5 of WFS1 gene. This mutation wasn’t present in 100 Portuguese hearing controls later sequenced. Two cases of Pendred Syndrome were studied. No mutation was found in the relevant exons analysed. So, the genetic cause couldn´t yet be determined. This study represents a contribution for extending the knowledge on hereditary HL in the Portuguese population, either in the identification of the genetic etiology in affected families, or in the development of more accurate diagnostic protocols. |
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