GJB2: The spectrum of deafness-causing allele variants and their phenotype
| Autor: | Sai Prasad, G. Parker Chamberlin, Guy Van Camp, R. Thomas Taggart, Richard J.H. Smith, Ignacio del Castillo, Hela Azaiez, Chelsea L. Welp, Stephanie M. Fischer |
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| Rok vydání: | 2004 |
| Předmět: |
Genotype
DNA Mutational Analysis Nonsense mutation Genes Recessive Penetrance Deafness medicine.disease_cause Sensitivity and Specificity Connexins Hearing Loss Bilateral Genetic Heterogeneity Gene Frequency otorhinolaryngologic diseases Genetics medicine Humans Missense mutation Genetic Testing Allele Allele frequency Alleles Chromatography High Pressure Liquid Polymorphism Single-Stranded Conformational Genetics (clinical) Sequence Deletion Mutation biology Genetic heterogeneity Exons Sequence Analysis DNA Molecular biology Connexin 26 Phenotype biology.protein Audiometry Pure-Tone GJB6 |
| Zdroj: | Human mutation |
| ISSN: | 1098-1004 1059-7794 |
| Popis: | Genetic testing was completed on 1,294 persons with deafness referred to the Molecular Otolaryngology Research Laboratories to establish a diagnosis of DFNB1. Exon 2 of GJB2 was screened for coding sequence allele variants by denaturing high-performance liquid chromatography (DHPLC) complemented by bidirectional sequencing. If two deafness-causing mutations of GJB2 (encoding Connexin 26) were identified, further screening was not performed. If only a single deafness-causing mutation was identified, we screened for the g.1777179_2085947del (hereafter called del(GJB6-D13S1830); GenBank NT_024524.13) and mutations in the noncoding region of GJB2. Phenotype-genotype correlations were evaluated by categorizing mutations as either protein truncating or nontruncating. A total of 205 persons carried two GJB2 exon 2 mutations and were diagnosed as having DFNB1; 100 persons carried only a single deafness-causing allele variant of exon 2. A total of 37 of these persons were c.35delG carriers, and 51 carried other allele variants of GJB2. Persons diagnosed with DFNB1 segregating two truncating/nonsense mutations had a more severe phenotype than persons carrying two missense mutations, with mean hearing impairments being 88 and 37%, respectively (P < 0.05). The number of deaf c.35delG carriers was greater than expected when compared to the c.35delG carrier frequency in normal-hearing controls (P < 0.05), suggesting the existence of at least one other mutation outside the GJB2 coding region that does not complement GJB2 deafness-causing allele variants. |
| Databáze: | OpenAIRE |
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