#603622
Table of Contents
A number sign (#) is used with this entry because autosomal dominant deafness-17 (DFNA17) is caused by heterozygous mutation in the MYH9 gene (160775) on chromosome 22q12.
Lalwani et al. (1999) studied a 5-generation American family, previously reported by Lalwani et al. (1997), with deafness caused by cochleosaccular degeneration (CSD). CSD is the most common histopathologic finding in cases of profound congenital deafness and is estimated to occur in approximately 70% of cases. CSD was first described by Scheibe (1892) and is commonly known as Scheibe dysplasia. It affects structures that are derived from the pars inferior of the otocyst. Thus, the membranous cochlea and saccule are affected, but the osseous labyrinth, the membranous utricle, and the semicircular canals are normal. The family studied by Lalwani et al. (1997, 1999) had been identified through a temporal bone database; because there is no clinically available test to diagnose CSD, postmortem histologic examination of the temporal bone is required. The affected family members exhibited nonsyndromic hearing loss with an autosomal dominant mode of transmission; there was no pigmentary abnormality. The hearing impairment began at age 10 years and involved only the high frequencies; by the third decade of life, affected family members had moderate to severe deafness.
Hildebrand et al. (2006) reported a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17. The self-reported age of onset ranged from 6 years to the mid-twenties. The hearing loss was progressive with a general trend of initial mild high-frequency loss during childhood and adolescence and with a flattening of the audiogram over time. The hearing loss became severe to profound by the second to third decades, although there was some intrafamilial variability.
Dantas et al. (2014) reported a Brazilian family in which 10 members had autosomal dominant progressive bilateral hearing loss affecting all frequencies, with age of onset ranging from the first to the fifth decade. Three other family members had a distinct hearing loss phenotype, affecting only high frequencies with onset at about age 40.
Hildebrand et al. (2006) reported that 5 individuals in their Australian family received cochlear implants with excellent results and noted the contrast between the results of cochlear implant in their family and the poor results after cochlear implant reported in 1 patient from the family of Lalwani et al. (2000). Hildebrand et al. (2006) speculated that early intervention plays an important role in the therapeutic response.
Lalwani et al. (1999) mapped the nonsyndromic hereditary hearing impairment in the family studied by them to chromosome 22q12.2-q13.3 by linkage analysis.
In a Brazilian family in which 10 members had hearing loss at all frequencies and 3 others had hearing loss at high frequencies, Dantas et al. (2014) found linkage to chromosome 14 (lod = 2.1) and to chromosome 22 (lod = 1.9).
DFNA17 maps to the same region as MYH9 (160775), a nonmuscle-myosin heavy-chain gene. Because of the importance of myosins in hearing, Lalwani et al. (2000) tested MYH9 as a candidate gene for DFNA17. Expression of MYH9 in the rat cochlea was confirmed using RT-PCR and immunohistochemistry analysis. MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane. Sequence analysis of MYH9 in the family previously studied by Lalwani et al. (1997, 1999) demonstrated that a heterozygous mutation (R705H; 160775.0008) cosegregated with deafness.
In affected members of a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17, Hildebrand et al. (2006) identified a heterozygous R705H mutation in the MYH9 gene.
In a Brazilian family in which 10 members had nonsyndromic hearing loss at all frequencies, Dantas et al. (2014) identified heterozygosity for the same R705H mutation in the MYH9 gene. The mutation segregated with the phenotype in the family. Three other members of this family with hearing loss at high frequencies did not have the mutation.
Dantas, V. G. L., Lezirovitz, K., Yamamoto, G. L., Moura de Souza, C. F., Ferreira, S. G., Mingroni-Netto, R. C. c.G2114A MYH9 mutation (DFNA17) causes non-syndromic autosomal dominant hearing loss in a Brazilian family. Genet. Molec. Biol. 37: 616-621, 2014. [PubMed: 25505834, related citations] [Full Text]
Hildebrand, M. S., de Silva, M. G., Gardner, R. J. M., Rose, E., de Graaf, C. A., Bahlo, M., Dahl, H.-H. M. Cochlear implants for DFNA17 deafness. Laryngoscope 116: 2211-2215, 2006. [PubMed: 17146397, related citations] [Full Text]
Lalwani, A. K., Goldstein, J. A., Kelley, M. J., Luxford, W., Castelein, C. M., Mhatre, A. N. Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9. Am. J. Hum. Genet. 67: 1121-1128, 2000. [PubMed: 11023810, images, related citations] [Full Text]
Lalwani, A. K., Linthicum, F. H., Wilcox, E. R., Moore, J. K., Walters, F. C., San Agustin, T. B., Mislinski, J., Miller, M. R., Sinninger, Y., Attaie, A., Luxford, W. M. A five-generation family with late-onset progressive hereditary hearing impairment due to cochleosaccular degeneration. Audiol. Neurootol. 2: 139-154, 1997. [PubMed: 9390828, related citations] [Full Text]
Lalwani, A. K., Luxford, W. M., Mhatre, A. N., Attaie, A., Wilcox, E. R., Castelein, C. M. A new locus for nonsyndromic hereditary hearing impairment, DFNA17, maps to chromosome 22 and represents a gene for cochleosaccular degeneration. (Letter) Am. J. Hum. Genet. 64: 318-323, 1999. [PubMed: 9915977, related citations] [Full Text]
Scheibe, A. A case of deaf-mutism, with auditory atrophy and anomalies of development in the membranous labyrinth of both ears. Arch. Otolaryng. 21: 12-22, 1892.
Other entities represented in this entry:
ORPHA: 90635; DO: 0110548;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 22q12.3 | Deafness, autosomal dominant 17 | 603622 | Autosomal dominant | 3 | MYH9 | 160775 |
A number sign (#) is used with this entry because autosomal dominant deafness-17 (DFNA17) is caused by heterozygous mutation in the MYH9 gene (160775) on chromosome 22q12.
Lalwani et al. (1999) studied a 5-generation American family, previously reported by Lalwani et al. (1997), with deafness caused by cochleosaccular degeneration (CSD). CSD is the most common histopathologic finding in cases of profound congenital deafness and is estimated to occur in approximately 70% of cases. CSD was first described by Scheibe (1892) and is commonly known as Scheibe dysplasia. It affects structures that are derived from the pars inferior of the otocyst. Thus, the membranous cochlea and saccule are affected, but the osseous labyrinth, the membranous utricle, and the semicircular canals are normal. The family studied by Lalwani et al. (1997, 1999) had been identified through a temporal bone database; because there is no clinically available test to diagnose CSD, postmortem histologic examination of the temporal bone is required. The affected family members exhibited nonsyndromic hearing loss with an autosomal dominant mode of transmission; there was no pigmentary abnormality. The hearing impairment began at age 10 years and involved only the high frequencies; by the third decade of life, affected family members had moderate to severe deafness.
Hildebrand et al. (2006) reported a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17. The self-reported age of onset ranged from 6 years to the mid-twenties. The hearing loss was progressive with a general trend of initial mild high-frequency loss during childhood and adolescence and with a flattening of the audiogram over time. The hearing loss became severe to profound by the second to third decades, although there was some intrafamilial variability.
Dantas et al. (2014) reported a Brazilian family in which 10 members had autosomal dominant progressive bilateral hearing loss affecting all frequencies, with age of onset ranging from the first to the fifth decade. Three other family members had a distinct hearing loss phenotype, affecting only high frequencies with onset at about age 40.
Hildebrand et al. (2006) reported that 5 individuals in their Australian family received cochlear implants with excellent results and noted the contrast between the results of cochlear implant in their family and the poor results after cochlear implant reported in 1 patient from the family of Lalwani et al. (2000). Hildebrand et al. (2006) speculated that early intervention plays an important role in the therapeutic response.
Lalwani et al. (1999) mapped the nonsyndromic hereditary hearing impairment in the family studied by them to chromosome 22q12.2-q13.3 by linkage analysis.
In a Brazilian family in which 10 members had hearing loss at all frequencies and 3 others had hearing loss at high frequencies, Dantas et al. (2014) found linkage to chromosome 14 (lod = 2.1) and to chromosome 22 (lod = 1.9).
DFNA17 maps to the same region as MYH9 (160775), a nonmuscle-myosin heavy-chain gene. Because of the importance of myosins in hearing, Lalwani et al. (2000) tested MYH9 as a candidate gene for DFNA17. Expression of MYH9 in the rat cochlea was confirmed using RT-PCR and immunohistochemistry analysis. MYH9 was immunolocalized in the organ of Corti, the subcentral region of the spiral ligament, and the Reissner membrane. Sequence analysis of MYH9 in the family previously studied by Lalwani et al. (1997, 1999) demonstrated that a heterozygous mutation (R705H; 160775.0008) cosegregated with deafness.
In affected members of a 5-generation Australian family of Anglo Celtic origin with nonsyndromic DFNA17, Hildebrand et al. (2006) identified a heterozygous R705H mutation in the MYH9 gene.
In a Brazilian family in which 10 members had nonsyndromic hearing loss at all frequencies, Dantas et al. (2014) identified heterozygosity for the same R705H mutation in the MYH9 gene. The mutation segregated with the phenotype in the family. Three other members of this family with hearing loss at high frequencies did not have the mutation.
Dantas, V. G. L., Lezirovitz, K., Yamamoto, G. L., Moura de Souza, C. F., Ferreira, S. G., Mingroni-Netto, R. C. c.G2114A MYH9 mutation (DFNA17) causes non-syndromic autosomal dominant hearing loss in a Brazilian family. Genet. Molec. Biol. 37: 616-621, 2014. [PubMed: 25505834] [Full Text: https://doi.org/10.1590/S1415-47572014005000025]
Hildebrand, M. S., de Silva, M. G., Gardner, R. J. M., Rose, E., de Graaf, C. A., Bahlo, M., Dahl, H.-H. M. Cochlear implants for DFNA17 deafness. Laryngoscope 116: 2211-2215, 2006. [PubMed: 17146397] [Full Text: https://doi.org/10.1097/01.mlg.0000242089.72880.f8]
Lalwani, A. K., Goldstein, J. A., Kelley, M. J., Luxford, W., Castelein, C. M., Mhatre, A. N. Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9. Am. J. Hum. Genet. 67: 1121-1128, 2000. [PubMed: 11023810] [Full Text: https://doi.org/10.1016/S0002-9297(07)62942-5]
Lalwani, A. K., Linthicum, F. H., Wilcox, E. R., Moore, J. K., Walters, F. C., San Agustin, T. B., Mislinski, J., Miller, M. R., Sinninger, Y., Attaie, A., Luxford, W. M. A five-generation family with late-onset progressive hereditary hearing impairment due to cochleosaccular degeneration. Audiol. Neurootol. 2: 139-154, 1997. [PubMed: 9390828] [Full Text: https://doi.org/10.1159/000259237]
Lalwani, A. K., Luxford, W. M., Mhatre, A. N., Attaie, A., Wilcox, E. R., Castelein, C. M. A new locus for nonsyndromic hereditary hearing impairment, DFNA17, maps to chromosome 22 and represents a gene for cochleosaccular degeneration. (Letter) Am. J. Hum. Genet. 64: 318-323, 1999. [PubMed: 9915977] [Full Text: https://doi.org/10.1086/302216]
Scheibe, A. A case of deaf-mutism, with auditory atrophy and anomalies of development in the membranous labyrinth of both ears. Arch. Otolaryng. 21: 12-22, 1892.
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