#601316
Table of Contents
A number sign (#) is used with this entry because autosomal dominant deafness-10 (DFNA10) is caused by heterozygous mutation in the EYA4 gene (603550) on chromosome 6q23.
O'Neill et al. (1996) reported a large multigenerational family from the U.S. with progressive sensorineural hearing loss beginning in the second to fifth decades and leading ultimately to severe to profound hearing impairment requiring the use of amplification.
Verhoeven et al. (2000) reported a Belgian and a Norwegian family with nonsyndromic deafness similar to that in the American family reported by O'Neill et al. (1996). Hearing loss in all 3 families began with the middle frequencies and later involved the low and high frequencies.
O'Neill et al. (1996) mapped a locus for autosomal dominant late-onset progressive nonsyndromic hearing loss, designated DFNA10, to chromosome 6q22.2-q23.3 on the basis of linkage analysis in a large multigenerational family from the U.S. The markers D6S472 and D6S407 yielded 2-point lod scores of 4.44 and 4.0 at theta = 0, respectively. Multipoint linkage analysis of DFNA10 within a 5-marker linkage map yielded a maximum lod score of 5.27 with marker D6S407.
By extending the American pedigree in which linkage of DFNA10 to 6q was first demonstrated (O'Neill et al., 1996), and by study of a Belgian and a Norwegian family with DFNA10, Verhoeven et al. (2000) corroborated and narrowed the linkage to a 3.7-cM region.
Hildebrand et al. (2007) performed a genomewide scan on 10 affected members of a 5-generation Australian family with nonsyndromic sensorineural hearing loss and obtained a maximum lod score of 2.5 for an 8-cM critical region on chromosome 6 containing the DFNA10 locus.
Wayne et al. (2001) identified 'eyes absent' 4 (EYA4; 603550), a member of the vertebrate Eya family of transcriptional activators, as the causative gene of autosomal dominant postlingual progressive hearing loss at the DFNA10 locus. In affected members of 2 unrelated families from Belgium and the U.S. segregating for deafness, previously studied by Verhoeven et al. (2000) and shown to link to this locus, Wayne et al. (2001) identified heterozygosity for 2 different mutations in EYA4 (603550.0001 and 603550.0002, respectively), both of which create premature stop codons. Although EYA proteins interact with members of the SIX (601205) and DACH (603803) protein families in a conserved network that regulates early embryonic development, this finding shows that EYA4 is also important postdevelopmentally for continued function of the mature organ of Corti.
In affected members of a family segregating autosomal dominant postlingual progressive sensorineural hearing loss, Makishima et al. (2007) identified heterozygosity for a 2-bp insertion (603550.0004) in the EYA4 gene. Comprehensive cardiac evaluation of 9 affected individuals revealed no evidence of dilated cardiomyopathy. Noting that the 3 known EYA4 mutations causing nonsyndromic SNHL are predicted to encode truncated EYA proteins with a deleted Eya domain but an intact variable domain, whereas the EYA4 deletion (603550.0003) causing syndromic hearing loss with dilated cardiomyopathy (CMD1J; 605362) partially truncates the variable domain of the protein as well, Makishima et al. (2007) proposed a correlation between EYA4 mutation position and the presence or absence of DCM.
In affected members of a 5-generation Australian family with nonsyndromic sensorineural hearing loss mapping to the DFNA10 locus, Hildebrand et al. (2007) identified heterozygosity for a splice site mutation (603550.0005) in the EYA4 gene.
Hildebrand, M. S., Coman, D., Yang, T., Gardner, R. J. M., Rose, E., Smith, R. J. H., Bahlo, M., Dahl, H.-H. M. A novel splice site mutation in EYA4 causes DFNA10 hearing loss. Am. J. Med. Genet. 143A: 1599-1604, 2007. Note: Erratum: Am. J. Med. Genet. 146A: 1099 only, 2008. [PubMed: 17568404, related citations] [Full Text]
Makishima, T., Madeo, A. C., Brewer, C. C., Zalewski, C. K., Butman, J. A., Sachdev, V., Arai, A. E., Holbrook, B. M., Rosing, D. R., Griffith, A. J. Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain. Am. J. Med. Genet. 143A: 1592-1598, 2007. [PubMed: 17567890, related citations] [Full Text]
O'Neill, M. E., Marietta, J., Nishimura, D., Wayne, S., Van Camp, G., Van Laer, L., Negrini, C., Wilcox, E. R., Chen, A., Fukushima, K., Ni, L., Sheffield, V. C., Smith, R. J. H. A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6. Hum. Molec. Genet. 5: 853-856, 1996. [PubMed: 8776603, related citations] [Full Text]
Verhoeven, K., Fagerheim, T., Prasad, S., Wayne, S., De Clau, F., Balemans, W., Verstreken, M., Schatteman, I., Solem, B., Van de Heyning, P., Tranebjarg, L., Smith, R. J. H., Van Camp, G. Refined localization and two additional linked families for the DFNA10 locus for nonsyndromic hearing impairment. Hum. Genet. 107: 7-11, 2000. [PubMed: 10982027, related citations] [Full Text]
Wayne, S., Robertson, N. G., DeClau, F., Chen, N., Verhoeven, K., Prasad, S., Tranebjarg, L., Morton, C. C., Ryan, A. F., Van Camp, G., Smith, R. J. H. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum. Molec. Genet. 10: 195-200, 2001. [PubMed: 11159937, related citations] [Full Text]
ORPHA: 90635; DO: 0110542;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 6q23.2 | Deafness, autosomal dominant 10 | 601316 | Autosomal dominant | 3 | EYA4 | 603550 |
A number sign (#) is used with this entry because autosomal dominant deafness-10 (DFNA10) is caused by heterozygous mutation in the EYA4 gene (603550) on chromosome 6q23.
O'Neill et al. (1996) reported a large multigenerational family from the U.S. with progressive sensorineural hearing loss beginning in the second to fifth decades and leading ultimately to severe to profound hearing impairment requiring the use of amplification.
Verhoeven et al. (2000) reported a Belgian and a Norwegian family with nonsyndromic deafness similar to that in the American family reported by O'Neill et al. (1996). Hearing loss in all 3 families began with the middle frequencies and later involved the low and high frequencies.
O'Neill et al. (1996) mapped a locus for autosomal dominant late-onset progressive nonsyndromic hearing loss, designated DFNA10, to chromosome 6q22.2-q23.3 on the basis of linkage analysis in a large multigenerational family from the U.S. The markers D6S472 and D6S407 yielded 2-point lod scores of 4.44 and 4.0 at theta = 0, respectively. Multipoint linkage analysis of DFNA10 within a 5-marker linkage map yielded a maximum lod score of 5.27 with marker D6S407.
By extending the American pedigree in which linkage of DFNA10 to 6q was first demonstrated (O'Neill et al., 1996), and by study of a Belgian and a Norwegian family with DFNA10, Verhoeven et al. (2000) corroborated and narrowed the linkage to a 3.7-cM region.
Hildebrand et al. (2007) performed a genomewide scan on 10 affected members of a 5-generation Australian family with nonsyndromic sensorineural hearing loss and obtained a maximum lod score of 2.5 for an 8-cM critical region on chromosome 6 containing the DFNA10 locus.
Wayne et al. (2001) identified 'eyes absent' 4 (EYA4; 603550), a member of the vertebrate Eya family of transcriptional activators, as the causative gene of autosomal dominant postlingual progressive hearing loss at the DFNA10 locus. In affected members of 2 unrelated families from Belgium and the U.S. segregating for deafness, previously studied by Verhoeven et al. (2000) and shown to link to this locus, Wayne et al. (2001) identified heterozygosity for 2 different mutations in EYA4 (603550.0001 and 603550.0002, respectively), both of which create premature stop codons. Although EYA proteins interact with members of the SIX (601205) and DACH (603803) protein families in a conserved network that regulates early embryonic development, this finding shows that EYA4 is also important postdevelopmentally for continued function of the mature organ of Corti.
In affected members of a family segregating autosomal dominant postlingual progressive sensorineural hearing loss, Makishima et al. (2007) identified heterozygosity for a 2-bp insertion (603550.0004) in the EYA4 gene. Comprehensive cardiac evaluation of 9 affected individuals revealed no evidence of dilated cardiomyopathy. Noting that the 3 known EYA4 mutations causing nonsyndromic SNHL are predicted to encode truncated EYA proteins with a deleted Eya domain but an intact variable domain, whereas the EYA4 deletion (603550.0003) causing syndromic hearing loss with dilated cardiomyopathy (CMD1J; 605362) partially truncates the variable domain of the protein as well, Makishima et al. (2007) proposed a correlation between EYA4 mutation position and the presence or absence of DCM.
In affected members of a 5-generation Australian family with nonsyndromic sensorineural hearing loss mapping to the DFNA10 locus, Hildebrand et al. (2007) identified heterozygosity for a splice site mutation (603550.0005) in the EYA4 gene.
Hildebrand, M. S., Coman, D., Yang, T., Gardner, R. J. M., Rose, E., Smith, R. J. H., Bahlo, M., Dahl, H.-H. M. A novel splice site mutation in EYA4 causes DFNA10 hearing loss. Am. J. Med. Genet. 143A: 1599-1604, 2007. Note: Erratum: Am. J. Med. Genet. 146A: 1099 only, 2008. [PubMed: 17568404] [Full Text: https://doi.org/10.1002/ajmg.a.31860]
Makishima, T., Madeo, A. C., Brewer, C. C., Zalewski, C. K., Butman, J. A., Sachdev, V., Arai, A. E., Holbrook, B. M., Rosing, D. R., Griffith, A. J. Nonsyndromic hearing loss DFNA10 and a novel mutation of EYA4: evidence for correlation of normal cardiac phenotype with truncating mutations of the Eya domain. Am. J. Med. Genet. 143A: 1592-1598, 2007. [PubMed: 17567890] [Full Text: https://doi.org/10.1002/ajmg.a.31793]
O'Neill, M. E., Marietta, J., Nishimura, D., Wayne, S., Van Camp, G., Van Laer, L., Negrini, C., Wilcox, E. R., Chen, A., Fukushima, K., Ni, L., Sheffield, V. C., Smith, R. J. H. A gene for autosomal dominant late-onset progressive non-syndromic hearing loss, DFNA10, maps to chromosome 6. Hum. Molec. Genet. 5: 853-856, 1996. [PubMed: 8776603] [Full Text: https://doi.org/10.1093/hmg/5.6.853]
Verhoeven, K., Fagerheim, T., Prasad, S., Wayne, S., De Clau, F., Balemans, W., Verstreken, M., Schatteman, I., Solem, B., Van de Heyning, P., Tranebjarg, L., Smith, R. J. H., Van Camp, G. Refined localization and two additional linked families for the DFNA10 locus for nonsyndromic hearing impairment. Hum. Genet. 107: 7-11, 2000. [PubMed: 10982027] [Full Text: https://doi.org/10.1007/s004390000319]
Wayne, S., Robertson, N. G., DeClau, F., Chen, N., Verhoeven, K., Prasad, S., Tranebjarg, L., Morton, C. C., Ryan, A. F., Van Camp, G., Smith, R. J. H. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum. Molec. Genet. 10: 195-200, 2001. [PubMed: 11159937] [Full Text: https://doi.org/10.1093/hmg/10.3.195]
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