#605192
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-23 (DFNA23) is caused by heterozygous mutation in the SIX1 gene (605192) on chromosome 14q23.
Salam et al. (2000) studied DNA samples from 22 members of a Swiss-German kindred in 3 generations: 10 with hearing impairment, 8 unaffected, and 4 spouses of hearing-impaired pedigree members. The hearing-impaired family members had prelingual bilateral symmetric hearing loss. All audiograms from the hearing-impaired individuals displayed sloping curves, with hearing ability ranging from normal hearing to mild hearing loss in low frequencies, normal hearing to profound hearing loss in mid-frequencies, and moderate to profound hearing loss in high frequencies. A conductive component existed for 50% of the hearing-impaired family members. Most of the hearing-impaired family members did not display progression of hearing loss.
Mosrati et al. (2011) reported a Tunisian family (KH) with bilateral moderate to profound hearing impairment. Hearing loss was both mixed and sensorineural, and some individuals had bilateral or unilateral preauricular pits. No other anomalies, such as branchial arch remnants, were observed. Temporal bone computed tomography in 3 affected individuals showed no inner ear malformations. No kidney malformations were found on renal ultrasound of the patients.
By linkage analysis, Salam et al. (2000) mapped the deafness locus (DFNA23) in this family to 14q21-q22, with a maximum multipoint lod score of 5.1 at marker D14S290.
In an affected member (IV:5) of the family reported by Salam et al. (2000), Ruf et al. (2004) identified a heterozygous mutation in the SIX1 gene (601205.0003). The patient was also found to have a solitary left hypodysplastic kidney with vesicoureteral reflux and progressive renal failure, suggesting that this family may have BOR/BO syndrome (see 608389).
In affected members of a Tunisian family with autosomal dominant nonsyndromic hearing impairment showing linkage to 14q23, Mosrati et al. (2011) identified a heterozygous missense mutation in the SIX1 gene (601205.0005). The mutation segregated with the phenotype in the family.
Mosrati, M. A., Hammami, B., Rebeh, I. B., Ayadi, L., Dhouib, L., Ben Mahfoudh, K., Hakim, B., Charfeddine, I., Mnif, J., Ghorbel, A., Masmoudi, S. A novel dominant mutation in SIX1, affecting a highly conserved residue, result (sic) in only auditory defects in humans. Europ. J. Med. Genet. 54: e484-e488, 2011. Note: Electronic Article. [PubMed: 21700001, related citations] [Full Text]
Ruf, R. G., Xu, P.-X., Silvius, D., Otto, E. A., Beekmann, F., Muerb, U. T., Kumar, S., Neuhaus, T. J., Kemper, M. J., Raymond, R. M., Jr., Brophy, P. D., Berkman, J., and 10 others. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc. Nat. Acad. Sci. 101: 8090-8095, 2004. [PubMed: 15141091, images, related citations] [Full Text]
Salam, A. A., Hafner, F. M., Linder, T. E., Spillmann, T., Schinzel, A. A., Leal, S. M. A novel locus (DFNA23) for prelingual autosomal dominant nonsyndromic hearing loss maps to 14q21-q22 in a Swiss German kindred. Am. J. Hum. Genet. 66: 1984-1988, 2000. [PubMed: 10777717, related citations] [Full Text]
ORPHA: 90635; DO: 0110553;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 14q23.1 | Deafness, autosomal dominant 23 | 605192 | Autosomal dominant | 3 | SIX1 | 601205 |
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-23 (DFNA23) is caused by heterozygous mutation in the SIX1 gene (605192) on chromosome 14q23.
Salam et al. (2000) studied DNA samples from 22 members of a Swiss-German kindred in 3 generations: 10 with hearing impairment, 8 unaffected, and 4 spouses of hearing-impaired pedigree members. The hearing-impaired family members had prelingual bilateral symmetric hearing loss. All audiograms from the hearing-impaired individuals displayed sloping curves, with hearing ability ranging from normal hearing to mild hearing loss in low frequencies, normal hearing to profound hearing loss in mid-frequencies, and moderate to profound hearing loss in high frequencies. A conductive component existed for 50% of the hearing-impaired family members. Most of the hearing-impaired family members did not display progression of hearing loss.
Mosrati et al. (2011) reported a Tunisian family (KH) with bilateral moderate to profound hearing impairment. Hearing loss was both mixed and sensorineural, and some individuals had bilateral or unilateral preauricular pits. No other anomalies, such as branchial arch remnants, were observed. Temporal bone computed tomography in 3 affected individuals showed no inner ear malformations. No kidney malformations were found on renal ultrasound of the patients.
By linkage analysis, Salam et al. (2000) mapped the deafness locus (DFNA23) in this family to 14q21-q22, with a maximum multipoint lod score of 5.1 at marker D14S290.
In an affected member (IV:5) of the family reported by Salam et al. (2000), Ruf et al. (2004) identified a heterozygous mutation in the SIX1 gene (601205.0003). The patient was also found to have a solitary left hypodysplastic kidney with vesicoureteral reflux and progressive renal failure, suggesting that this family may have BOR/BO syndrome (see 608389).
In affected members of a Tunisian family with autosomal dominant nonsyndromic hearing impairment showing linkage to 14q23, Mosrati et al. (2011) identified a heterozygous missense mutation in the SIX1 gene (601205.0005). The mutation segregated with the phenotype in the family.
Mosrati, M. A., Hammami, B., Rebeh, I. B., Ayadi, L., Dhouib, L., Ben Mahfoudh, K., Hakim, B., Charfeddine, I., Mnif, J., Ghorbel, A., Masmoudi, S. A novel dominant mutation in SIX1, affecting a highly conserved residue, result (sic) in only auditory defects in humans. Europ. J. Med. Genet. 54: e484-e488, 2011. Note: Electronic Article. [PubMed: 21700001] [Full Text: https://doi.org/10.1016/j.ejmg.2011.06.001]
Ruf, R. G., Xu, P.-X., Silvius, D., Otto, E. A., Beekmann, F., Muerb, U. T., Kumar, S., Neuhaus, T. J., Kemper, M. J., Raymond, R. M., Jr., Brophy, P. D., Berkman, J., and 10 others. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc. Nat. Acad. Sci. 101: 8090-8095, 2004. [PubMed: 15141091] [Full Text: https://doi.org/10.1073/pnas.0308475101]
Salam, A. A., Hafner, F. M., Linder, T. E., Spillmann, T., Schinzel, A. A., Leal, S. M. A novel locus (DFNA23) for prelingual autosomal dominant nonsyndromic hearing loss maps to 14q21-q22 in a Swiss German kindred. Am. J. Hum. Genet. 66: 1984-1988, 2000. [PubMed: 10777717] [Full Text: https://doi.org/10.1086/302931]
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