Alternative titles; symbols
ORPHA: 90635; DO: 0110544;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 11q23.3 | Deafness, autosomal dominant 8/12 | 601543 | Autosomal dominant | 3 | TECTA | 602574 |
A number sign (#) is used with this entry because of evidence that autosomal dominant nonsyndromic sensorineural deafness-12 (DFNA12), which has also been designated DFNA8, is caused by heterozygous mutation in the TECTA gene (602574) on chromosome 11q23.
Autosomal recessive deafness-21 (DFNB21; 603629) is an allelic disorder.
Kirschhofer et al. (1995, 1998) reported an Austrian family in which 11 individuals spanning 4 generations had autosomal dominant nonsyndromic sensorineural deafness. The hearing loss was moderate to severe, showed prelingual onset, and was relatively stable or nonprogressive. The degree of hearing impairment was similar in all affected members, regardless of age or sex. Pure tone audiometry showed hearing loss between 60 and 80 dB, with a maximum at 2,000 Hz (severe range 1,000 to 6,000 kHz) and a U-shaped curve. The disorder in this family was designated DFNA8. The studies indicated a cochlear lesion.
Verhoeven et al. (1997) reported a Belgian family with autosomal dominant mid-frequency (500 to 2,000 Hz) hearing loss with prelingual onset. There was no progression with age. Hearing loss ranged from mild to moderately severe. The disorder in this family was designated DFNA12.
Kirschhofer et al. (1998) contended that the phenotypes of the Austrian family reported by them and the Belgian family reported by Verhoeven et al. (1997) were slightly different. Whereas there was little interindividual variability in the Austrian family, the Belgian family showed interindividual variability. However, Mustapha et al. (1999) concluded that DFNA8 and DFNA12 represent the same form of autosomal dominant deafness.
Balciuniene et al. (1998, 1999) reported a large Swedish family with autosomal dominant nonsyndromic hearing loss of postlingual onset. Nine individuals had a more severe phenotype, with severe hearing loss with onset at a mean age of 9 years. Audiogram showed decreased hearing particularly at high frequencies (6 to 8 kHz) with up to an 80-dB drop at age 50. Some individuals had a milder phenotype, with mild hearing loss only at high frequencies (4 to 6 kHz) with a mean age of onset at 19 years. The hearing loss was progressive.
Moreno-Pelayo et al. (2001) reported a Spanish family in which 9 members had sensorineural nonsyndromic deafness. Onset was postlingual, occurring in the first or second decades. Audiometric testing showed mid frequency hearing loss, a U-shaped audiogram, and progressive hearing loss. Genetic analysis identified a heterozygous mutation in the TECTA gene (602574.0008).
Meyer et al. (2007) reported a family segregating 2 forms of deafness: autosomal dominant DFNA12 and autosomal recessive DFNB1A (220290). Analysis of audiograms by audioprofiling suggested that 2 sibs in the family had a different form of deafness compared to the others. Molecular genetic studies identified a heterozygous mutation in the TECTA gene (C1837R; 602574.0008) in those with mid to high frequency hearing loss, a U-shaped audiogram, and childhood onset; the 2 sibs with down-sloping high-frequency hearing loss and childhood onset were found to be compound heterozygous for 2 mutations in the GJB2 gene (L90P; 121011.0016 and V37I; 121011.0023). Meyer et al. (2007) emphasized the utility of audiogram profiling in heritable hearing loss to determine candidate gene involvement.
In initial studies of an Austrian family with autosomal dominant nonsyndromic sensorineural deafness, Kirschhofer et al. (1995) found linkage to a locus on chromosome 15q15-q21; this locus was designated DFNA8. However, in later publications, Kirschhofer et al. (1996, 1998) mapped the disorder in the same family to 11q and retained the DFNA8 designation for this family. Further studies yielded a maximum lod score of 3.6 at marker D11S934 on 11q; the lod score for the locus on chromosome 15 was reduced to 1.81.
By linkage analysis of a Belgian family with autosomal dominant hearing loss, Verhoeven et al. (1997) identified a candidate locus, designated DFNA12, on chromosome 11q22-q24 (lod scores in excess of 6.0). Analysis of key recombinants mapped the gene to a 36-cM interval on 11q22-q24, between markers D11S4120 and D11S912 (Verhoeven et al., 1997).
In a Swedish family with autosomal dominant nonsyndromic hearing loss of postlingual progressive type, Balciuniene et al. (1998) found evidence for linkage both to the DFNA12 region on 11q and to the DFNA2 region (600101) on 1p32. A detailed analysis of the phenotypes and haplotypes shared by the affected individual supported the notion that 2 genes segregated together with hearing impairment in the family. Severely affected family members had haplotypes linked to the disease allele on both chromosomes 1 and 11, whereas individuals with milder hearing loss had haplotypes linked to the disease allele on either chromosome 1 or chromosome 11. These observations suggested an additive effect of 2 genes, each gene resulting in a mild, sometimes undiagnosed, phenotype, together resulting in a more severe phenotype; this would be an example of digenic inheritance.
Van Camp et al. (1997) used the designation DFNA12 for the disorder in a Belgian family showing prelingual deafness and linkage to 11q22-q24.
In affected members of the Belgian family with DFNA12 reported by Verhoeven et al. (1997, 1997), Verhoeven et al. (1998) identified a heterozygous mutation in the TECTA gene (602574.0001).
In affected members of the Austrian family with DFNA8 reported by Kirschhofer et al. (1995, 1998), Verhoeven et al. (1998) identified a heterozygous mutation in the TECTA gene (Y1870C; 602574.0002).
In the kindred reported by Balciuniene et al. (1998), Balciuniene et al. (1999) identified a heterozygous mutation in the TECTA gene (C1057S; 602574.0004). The mutation was present in all severely affected individuals and in some mildly affected individuals.
Applying statistical analysis, Plantinga et al. (2006) found a significant association between TECTA mutations in the zona pellucida and zona adhesin domains and mid and high frequency hearing impairment, respectively. Cysteine-replacing mutations were associated with progressive hearing impairment.
Balciuniene, J., Dahl, N., Borg, E., Samuelsson, E., Koisti, M. J., Pettersson, U., Jazin, E. E. Evidence for digenic inheritance of nonsyndromic hereditary hearing loss in a Swedish family. Am. J. Hum. Genet. 63: 786-793, 1998. [PubMed: 9718342] [Full Text: https://doi.org/10.1086/302012]
Balciuniene, J., Dahl, N., Jalonen, P., Verhoeven, K., Van Camp, G., Borg, E., Pettersson, U., Jazin, E. E. Alpha-tectorin involvement in hearing disabilities: one gene--two phenotypes. Hum. Genet. 105: 211-216, 1999. [PubMed: 10987647] [Full Text: https://doi.org/10.1007/s004390051091]
Kirschhofer, K., Hoover, D. M., Kenyon, J. B., Franz, P., Weipoltshammer, K., Wachtler, F., Kimberling, W. J. Localisation of a gene responsible for an autosomal dominant non-syndromic sensorineural hearing loss to chromosome 15. Molecular Biology of Hearing and Deafness, Bethesda, Md. 1995.
Kirschhofer, K., Kenyon, J. B., Hoover, D. M., Franz, P., Weipoltshammer, K., Wachtler, F., Kimberling, W. J. Autosomal-dominant congenital severe sensorineural hearing loss: localisation of a disease gene to chromosome 11q by linkage analysis in an Austrian family. Second Workshop on the European Workgroup on Genetics of Hearing Impairment, Milan, Italy 1996.
Kirschhofer, K., Kenyon, J. B., Hoover, D. M., Franz, P., Weipoltshammer, K., Wachtler, F., Kimberling, W. J. Autosomal-dominant, prelingual, nonprogressive sensorineural hearing loss: localization of the gene (DFNA8) to chromosome 11q by linkage in an Austrian family. Cytogenet. Cell Genet. 82: 126-130, 1998. [PubMed: 9763681] [Full Text: https://doi.org/10.1159/000015086]
Meyer, N. C., Nishimura, C. J., McMordie, S., Smith, R. J. H. Audioprofiling identifies TECTA and GJB2-related deafness segregating in a single extended pedigree. Clin. Genet. 72: 130-137, 2007. [PubMed: 17661817] [Full Text: https://doi.org/10.1111/j.1399-0004.2007.00828.x]
Moreno-Pelayo, M. A., del Castillo, I., Villamar, M., Romero, L., Hernandez-Calvin, F. J., Herraiz, C., Barbera, R., Navas, C., Moreno, F. A cysteine substitution in the zona pellucida domain of alpha-tectorin results in autosomal dominant, postlingual, progressive, mid frequency hearing loss in a Spanish family. (Letter) J. Med. Genet. 38: e13, 2001. Note: Electronic Article. [PubMed: 11333869] [Full Text: https://doi.org/10.1136/jmg.38.5.e13]
Mustapha, M., Weil, D., Chardenoux, S., Elias, S., El-Zir, E., Beckmann, J. S., Loiselet, J., Petit, C. An alpha-tectorin gene defect causes a newly identified autosomal recessive form of sensorineural pre-lingual non-syndromic deafness, DFNB21. Hum. Molec. Genet. 8: 409-412, 1999. [PubMed: 9949200] [Full Text: https://doi.org/10.1093/hmg/8.3.409]
Plantinga, R. F., de Brouwer, A. P. M., Huygen, P. L. M., Kunst, H. P. M., Kremer, H., Cremers, C. W. R. J. A novel TECTA mutation in a Dutch DFNA8/12 family confirms genotype-phenotype correlation. J. Assoc. Res. Otolaryng. 7: 173-181, 2006. [PubMed: 16718611] [Full Text: https://doi.org/10.1007/s10162-006-0033-z]
Van Camp, G., Willems, P. J., Smith, R. J. H. Nonsyndromic hearing impairment: unparalleled heterogeneity. Am. J. Hum. Genet. 60: 758-764, 1997. [PubMed: 9106521]
Verhoeven, K., Van Camp, G., Govaerts, P. J., Balemans, W., Schatteman, I., Van Laer, L., Smith, R. J. H., Van de Heyning, P., Somers, T., Offeciers, F. E., Willems, P. J. Linkage of autosomal dominant nonsyndromic hearing loss (DFNA12) to the long arm of chromosome 11. (Abstract) Medizinische Genetik 9: 9 only, 1997.
Verhoeven, K., Van Camp, G., Govaerts, P. J., Balemans, W., Schatteman, I., Verstreken, M., Van Laer, L., Smith, R. J. H., Brown, M. R., Van de Heyning, P. H., Somers, T., Offeciers, F. E., Willems, P. J. A gene for autosomal dominant nonsyndromic hearing loss (DFNA12) maps to chromosome 11q22-24. Am. J. Hum. Genet. 60: 1168-1173, 1997. [PubMed: 9150164]
Verhoeven, K., Van Laer, L., Kirschhofer, K., Legan, P. K., Hughes, D. C., Schatteman, I., Verstreken, M., Van Hauwe, P., Coucke, P., Chen, A., Smith, R. J. H., Somers, T., Offeciers, F. E., Van de Heyning, P., Richardson, G. P., Wachtler, F., Kimberling, W. J., Willems, P. J., Govaerts, P. J., Van Camp, G. Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment. Nature Genet. 19: 60-62, 1998. Note: Erratum: Nature Genet. 21: 449 only, 1999. [PubMed: 9590290] [Full Text: https://doi.org/10.1038/ng0598-60]