Genetic modifiers of hearing

Table 2. Genetic modifiers and digenic inheritance of hearing loss reported in mice and humans

Mouse

References

Human

References

Strain modifier and mutation:

  

Genetic modifier and mutation:

  

Modifier gene (locus)

Mutant gene

  

Modifier gene (locus)

Mutant gene

  

Cdh23753A/G (mdfw)

Atp2b2dfw-2J

[13,14]

ATP2B2

CDH23

[17]

Cdh23753A/G

Mass1frings

[9]

unknown (DFNM1)

DFNB26

[16]

Mtap1a (Moth1)

Tubtub

[7,8]

unknown, Chr 8

 MT-RNR1A1555G

[5]

unknown (Mead 1,2); Nxf1 (Mead3)

Eya1bor

[12, 23]

TFB1M ?, Chr 6

MT-RNR1A1555G

[4]

unknown (Tmc1m 1-4) Tmc1Bth

 [20]

 TRMUA10S MT-RNR1A1555G

[21]

unknown (Chr 7) Jag1del1

[22] 

inferred

MYO7A

[18]

       

Digenic inheritance:

  

Digenic inheritance:

  

mutant gene

mutant gene

  

mutant gene

mutant gene

  

Cdh23v

Pcdh15av

[19]

CDH23

PCDH15

[19]

Gjb2

Gjb6

[10]

GJB2

GJB6

[6,15]

Thratm2

Thrbtm1

[11]

GJB3

TECTA

[3]

     

GJB2

MT-RNR1A1555G

[1]

     

USH3

MYO7A

[2]

[1]           Abe, S., Kelley, P.M., Kimberling, W.J. and Usami, S.I., Connexin 26 gene (GJB2) mutation modulates the severity of hearing loss associated with the 1555A-->G mitochondrial mutation, Am J Med Genet, 103 (2001) 334-8.

[2]           Adato, A., Kalinski, H., Weil, D., Chaib, H., Korostishevsky, M. and Bonne-Tamir, B., Possible interaction between USH1B and USH3 gene products as implied by apparent digenic deafness inheritance, Am J Hum Genet, 65 (1999) 261-5.

[3]           Balciuniene, J., Dahl, N., Borg, E., Samuelsson, E., Koisti, M.J., Pettersson, U. and Jazin, E.E., Evidence for digenic inheritance of nonsyndromic hereditary hearing loss in a Swedish family, Am J Hum Genet, 63 (1998) 786-93.

[4]           Bykhovskaya, Y., Mengesha, E., Wang, D., Yang, H., Estivill, X., Shohat, M. and Fischel-Ghodsian, N., Human mitochondrial transcription factor B1 as a modifier gene for hearing loss associated with the mitochondrial A1555G mutation, Mol Genet Metab, 82 (2004) 27-32.

[5]           Bykhovskaya, Y., Yang, H., Taylor, K., Hang, T., Tun, R.Y., Estivill, X., Casano, R.A., Majamaa, K., Shohat, M. and Fischel-Ghodsian, N., Modifier locus for mitochondrial DNA disease: linkage and linkage disequilibrium mapping of a nuclear modifier gene for maternally inherited deafness, Genet Med, 3 (2001) 177-80.

[6]           del Castillo, I., Villamar, M., Moreno-Pelayo, M.A., del Castillo, F.J., Alvarez, A., Telleria, D., Menendez, I. and Moreno, F., A deletion involving the connexin 30 gene in nonsyndromic hearing impairment, N Engl J Med, 346 (2002) 243-9.

[7]           Ikeda, A., Zheng, Q.Y., Rosenstiel, P., Maddatu, T., Zuberi, A.R., Roopenian, D.C., North, M.A., Naggert, J.K., Johnson, K.R. and Nishina, P.M., Genetic modification of hearing in tubby mice: evidence for the existence of a major gene (moth1) which protects tubby mice from hearing loss, Hum Mol Genet, 8 (1999) 1761-1767.

[8]           Ikeda, A., Zheng, Q.Y., Zuberi, A.R., Johnson, K.R., Naggert, J.K. and Nishina, P.M., Microtubule-associated protein 1A is a modifier of tubby hearing (moth1), Nat Genet, 30 (2002) 401-5.

[9]           Johnson, K.R., Zheng, Q.Y., Weston, M.D., Ptacek, L.J. and Noben-Trauth, K., The Mass1(frings) mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC, Genomics, 85 (2005) 582-90.

[10]         Michel, V., Hardelin, J.P. and Petit, C., Molecular mechanism of a frequent genetic form of deafness, N Engl J Med, 349 (2003) 716-7.

[11]         Ng, L., Rusch, A., Amma, L.L., Nordstrom, K., Erway, L.C., Vennstrom, B. and Forrest, D., Suppression of the deafness and thyroid dysfunction in Thrb-null mice by an independent mutation in the Thra thyroid hormone receptor alpha gene, Hum Mol Genet, 10 (2001) 2701-8.

[12]         Niu, H., Makmura, L., Shen, T., Sheth, S.S., Blair, K. and Friedman, R.A., Identification of two major loci that suppress hearing loss and cochlear dysmorphogenesis in Eya1(bor/bor) mice, Genomics (2006).

[13]         Noben-Trauth, K., Zheng, Q.Y. and Johnson, K.R., Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss, Nat Genet, 35 (2003) 21-23.

[14]         Noben-Trauth, K., Zheng, Q.Y., Johnson, K.R. and Nishina, P.M., mdfw:  A deafness susceptibility locus that interacts with deaf waddler (dfw). Genomics, 44 (1997) 266-272.

[15]         Pallares-Ruiz, N., Blanchet, P., Mondain, M., Claustres, M. and Roux, A.F., A large deletion including most of GJB6 in recessive non syndromic deafness: a digenic effect?, Eur J Hum Genet, 10 (2002) 72-6.

[16]         Riazuddin, S., Castelein, C.M., Ahmed, Z.M., Lalwani, A.K., Mastroianni, M.A., Naz, S., Smith, T.N., Liburd, N.A., Friedman, T.B., Griffith, A.J. and Wilcox, E.R., Dominant modifier DFNM1 suppresses recessive deafness DFNB26, Nat Genet, 26 (2000) 431-4.

[17]         Schultz, J.M., Yang, Y., Caride, A.J., Filoteo, A.G., Penheiter, A.R., Lagziel, A., Morell, R.J., Mohiddin, S.A., Fananapazir, L., Madeo, A.C., Penniston, J.T. and Griffith, A.J., Modification of human hearing loss by plasma-membrane calcium pump PMCA2, N Engl J Med, 352 (2005) 1557-64.

[18]         Street, V.A., Kallman, J.C. and Kiemele, K.L., Modifier controls severity of a novel dominant low-frequency MyosinVIIA (MYO7A) auditory mutation, J Med Genet, 41 (2004) e62.

[19]         Zheng, Q.Y., Yan, D., Ouyang, X.M., Du, L.L., Yu, H., Chang, B., Johnson, K.R. and Liu, X.Z., Digenic inheritance of deafness caused by mutations in genes encoding cadherin 23 and protocadherin 15 in mice and humans, Hum Mol Genet, 14 (2005) 103-11.

[20]         Noguchi, Y., Kurima, K., Makishima, T., Hrabe de Angelis, M., Fuchs, H., Frolenkov, G., Kitamura, K., and Griffith, A., Multiple quantitative trait loci modify cochlear hair cell degeneration in the Beethoven (Tmc1Bth) mouse model of progressive hearinig loss DFNA36, Genetics, 173 (2006) 2111-9.

[21]         Guan, M.X., Yan, Q., Li, X., Bykhovskaya, Y., Gallo-Teran, J., Hajek, P., Umeda, N., Zhao, H., Garrido, G., Mengesha, E., Suzuki, T., Castillo, I.D., Peters, J.L., Li, R., Qian, Y., Wang, X., Ballana, E., Shohat, M., Lu, J., Estivill, X., Watanabe, K. and Fischel-Ghodsian, N., Mutation in TRMU Related to Transfer RNA Modification Modulates the Phenotypic Expression of the Deafness-Associated Mitochondrial 12S Ribosomal RNA Mutations, Am J Hum Genet, 79 (2006) 291-302.

[22]         Kiernan, A.E., Li, R., Hawes, N.L., Churchill, G.A., and Gridley, T., Genetic background modifies inner ear and eye phenotypes of Jag1 heterozygous mice, Genetics, 177 (2007) 307-311. 

[23]         Niu, H., Li, X., Makmura, L., and Friedman, R.A., Mapping of genetic modifiers of Eya1 (bor/bor) in CAST/EiJ and BALB/cJ that suppress cochlear aplasia and associated deafness, Mamm Genome [Oct 4, 2008, Epub ahead of print]