#607453
Table of Contents
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-44 (DFNA44) is caused by heterozygous mutation in the CCDC50 gene (611051) on chromosome 3q28. One such family has been reported.
Modamio-Hoybjor et al. (2003) reported a 5-generation Spanish family in which 18 members had onset of moderate hearing loss, mainly affecting low-mid frequencies, between 6 and 10 years of age. Deafness later involved all frequencies and progressed to profound hearing loss in the sixth decade.
By linkage analysis, Modamio-Hoybjor et al. (2003) identified a novel DFNA locus on chromosome 3q28-q29 in a Spanish family with postlingual and progressive hearing loss. They narrowed the locus, DFNA44, to a 3-cM interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of 2 genes in this interval, claudin-16 (603959) and fibroblast growth factor-12 (601513), revealed no disease-causing mutations.
Modamio-Hoybjor et al. (2007) identified the CCDC50 gene within the critical linkage area and considered it a candidate gene for DFNA44 hearing loss, given that it is expressed in cochlea. Sequence analysis of all exons and flanking intronic sequences of CCDC50 in an affected subject revealed a heterozygous mutation in exon 11 (1394_1401dupCACGGCAT; 611051.0001). CCDC50 encodes Ymer, an effector of epidermal growth factor (EGF)-mediated cell signaling that is ubiquitously expressed in different organs and has been suggested to inhibit downregulation of an EGF receptor. Modamio-Hoybjor et al. (2007) suggested that DFNA44 hearing loss may result from a time-dependent disorganization of the microtubule-based cytoskeleton in the pillar cells and stria vascularis of the adult auditory system.
Modamio-Hoybjor, S., Mencia, A., Goodyear, R., del Castillo, I., Richardson, G., Moreno, F., Moreno-Pelayo, M. A. A mutation in CCDC50, a gene encoding an effector of epidermal growth factor-mediated cell signaling, causes progressive hearing loss. Am. J. Hum. Genet. 80: 1076-1089, 2007. [PubMed: 17503326, images, related citations] [Full Text]
Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Mencia, A., del Castillo, I., Chardenoux, S., Armenta, D., Lathrop, M., Petit, C., Moreno, F. A novel locus for autosomal dominant nonsyndromic hearing loss (DFNA44) maps to chromosome 3q28-29. Hum. Genet. 112: 24-28, 2003. [PubMed: 12483295, related citations] [Full Text]
ORPHA: 90635; DO: 0110569;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3q28 | ?Deafness, autosomal dominant 44 | 607453 | Autosomal dominant | 3 | CCDC50 | 611051 |
A number sign (#) is used with this entry because of evidence that autosomal dominant deafness-44 (DFNA44) is caused by heterozygous mutation in the CCDC50 gene (611051) on chromosome 3q28. One such family has been reported.
Modamio-Hoybjor et al. (2003) reported a 5-generation Spanish family in which 18 members had onset of moderate hearing loss, mainly affecting low-mid frequencies, between 6 and 10 years of age. Deafness later involved all frequencies and progressed to profound hearing loss in the sixth decade.
By linkage analysis, Modamio-Hoybjor et al. (2003) identified a novel DFNA locus on chromosome 3q28-q29 in a Spanish family with postlingual and progressive hearing loss. They narrowed the locus, DFNA44, to a 3-cM interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of 2 genes in this interval, claudin-16 (603959) and fibroblast growth factor-12 (601513), revealed no disease-causing mutations.
Modamio-Hoybjor et al. (2007) identified the CCDC50 gene within the critical linkage area and considered it a candidate gene for DFNA44 hearing loss, given that it is expressed in cochlea. Sequence analysis of all exons and flanking intronic sequences of CCDC50 in an affected subject revealed a heterozygous mutation in exon 11 (1394_1401dupCACGGCAT; 611051.0001). CCDC50 encodes Ymer, an effector of epidermal growth factor (EGF)-mediated cell signaling that is ubiquitously expressed in different organs and has been suggested to inhibit downregulation of an EGF receptor. Modamio-Hoybjor et al. (2007) suggested that DFNA44 hearing loss may result from a time-dependent disorganization of the microtubule-based cytoskeleton in the pillar cells and stria vascularis of the adult auditory system.
Modamio-Hoybjor, S., Mencia, A., Goodyear, R., del Castillo, I., Richardson, G., Moreno, F., Moreno-Pelayo, M. A. A mutation in CCDC50, a gene encoding an effector of epidermal growth factor-mediated cell signaling, causes progressive hearing loss. Am. J. Hum. Genet. 80: 1076-1089, 2007. [PubMed: 17503326] [Full Text: https://doi.org/10.1086/518311]
Modamio-Hoybjor, S., Moreno-Pelayo, M. A., Mencia, A., del Castillo, I., Chardenoux, S., Armenta, D., Lathrop, M., Petit, C., Moreno, F. A novel locus for autosomal dominant nonsyndromic hearing loss (DFNA44) maps to chromosome 3q28-29. Hum. Genet. 112: 24-28, 2003. [PubMed: 12483295] [Full Text: https://doi.org/10.1007/s00439-002-0836-x]
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