%614211
Table of Contents
Bonsch et al. (2009) reported a 4-generation German family with postlingual onset of nonsyndromic progressive sensorineural hearing loss. Affected individuals had onset in the second to third decade of life of hearing loss first affecting high frequencies and then affecting lower frequencies. The audiogram of older individuals was flat. Four patients reported tinnitus, but none had vestibular signs.
The transmission pattern of hearing loss in the family reported by Bonsch et al. (2009) was consistent with autosomal dominant inheritance.
By genomewide linkage analysis of a German family with autosomal dominant nonsyndromic hearing loss, Bonsch et al. (2009) identified a 6-cM locus, termed DFNA33, on chromosome 13q34-qter. A maximum 2-point lod score of 2.96 was obtained at marked D13S285, with a maximum multipoint lod score of 3.28 at 124.56 cM.
A reassessment by Vona et al. (2023) of haplotypes used by Bonsch et al. (2009) to map the DFNA33 interval, as well as analysis of an affected member of the original family, suggested that the DFNA33 locus may be inaccurate; see MOLECULAR GENETICS.
Using whole-exome sequencing, Vona et al. (2023) analyzed an affected member of the original DFNA33 pedigree who had not been reported by Bonsch et al. (2009) and did not identify any causative variants. Analysis of the ATP11A gene (605868), which maps within the DFNA33 interval and is mutant in autosomal dominant deafness (DFNA84; 619810), identified only a benign intronic variant. Vona et al. (2023) reassessed haplotypes used to define the DFNA33 locus and noted a triple recombination event in 1 individual and a double recombination event in 2 individuals, suggesting an error in genotyping. Vona et al. (2023) concluded that their evidence did not support ATP11A as being the causative gene for the DFNA33 locus, and that the DFNA33 disease interval may be inaccurate. They furthermore stated that, considering the size of the family, multilocus heterogeneity or the presence of phenocopies could not be excluded.
Bonsch, D., Schmidt, C.-M., Scheer, P., Bohlender, J., Neumann, C., Zehnhoff-Dinnesen, A., Deufel, T. Ein neuer Genort fur eine autosomal-dominante, nichtsyndromale Schwerhorigkeit (DFNA33) liegt auf Chromosom 13q34-qter. HNO 57: 371-376, 2009. [PubMed: 19183916, related citations] [Full Text]
Vona, B., Regele, S., Rad, A., Strenzke, N., Pater, J. A., Neumann, K., Sturm, M., Haack, T. B., Am Zehnhoff-Dinnesen, A. G. Unraveling haplotype errors in the DFNA33 locus. Front. Genet. 14: 1214736, 2023. [PubMed: 37671045, images, related citations] [Full Text]
ORPHA: 90635; DO: 0110562;
Bonsch et al. (2009) reported a 4-generation German family with postlingual onset of nonsyndromic progressive sensorineural hearing loss. Affected individuals had onset in the second to third decade of life of hearing loss first affecting high frequencies and then affecting lower frequencies. The audiogram of older individuals was flat. Four patients reported tinnitus, but none had vestibular signs.
The transmission pattern of hearing loss in the family reported by Bonsch et al. (2009) was consistent with autosomal dominant inheritance.
By genomewide linkage analysis of a German family with autosomal dominant nonsyndromic hearing loss, Bonsch et al. (2009) identified a 6-cM locus, termed DFNA33, on chromosome 13q34-qter. A maximum 2-point lod score of 2.96 was obtained at marked D13S285, with a maximum multipoint lod score of 3.28 at 124.56 cM.
A reassessment by Vona et al. (2023) of haplotypes used by Bonsch et al. (2009) to map the DFNA33 interval, as well as analysis of an affected member of the original family, suggested that the DFNA33 locus may be inaccurate; see MOLECULAR GENETICS.
Using whole-exome sequencing, Vona et al. (2023) analyzed an affected member of the original DFNA33 pedigree who had not been reported by Bonsch et al. (2009) and did not identify any causative variants. Analysis of the ATP11A gene (605868), which maps within the DFNA33 interval and is mutant in autosomal dominant deafness (DFNA84; 619810), identified only a benign intronic variant. Vona et al. (2023) reassessed haplotypes used to define the DFNA33 locus and noted a triple recombination event in 1 individual and a double recombination event in 2 individuals, suggesting an error in genotyping. Vona et al. (2023) concluded that their evidence did not support ATP11A as being the causative gene for the DFNA33 locus, and that the DFNA33 disease interval may be inaccurate. They furthermore stated that, considering the size of the family, multilocus heterogeneity or the presence of phenocopies could not be excluded.
Bonsch, D., Schmidt, C.-M., Scheer, P., Bohlender, J., Neumann, C., Zehnhoff-Dinnesen, A., Deufel, T. Ein neuer Genort fur eine autosomal-dominante, nichtsyndromale Schwerhorigkeit (DFNA33) liegt auf Chromosom 13q34-qter. HNO 57: 371-376, 2009. [PubMed: 19183916] [Full Text: https://doi.org/10.1007/s00106-008-1832-9]
Vona, B., Regele, S., Rad, A., Strenzke, N., Pater, J. A., Neumann, K., Sturm, M., Haack, T. B., Am Zehnhoff-Dinnesen, A. G. Unraveling haplotype errors in the DFNA33 locus. Front. Genet. 14: 1214736, 2023. [PubMed: 37671045] [Full Text: https://doi.org/10.3389/fgene.2023.1214736]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM