Abstract
Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of vertigo, tinnitus and fluctuating sensorineural hearing loss. Most MD cases are sporadic, but 5–15% of patients are familial following an autosomal dominant mode of inheritance with incomplete penetrance. We have previously identified a candidate gene region for MD on chromosome 12p12.3 using linkage analysis. We genotyped 15 Swedish families segregating familial MD (FMD) to further clarify the role of chromosome 12p in a larger cohort of families. Highly polymorphic marker loci were analyzed over the 16-Mb candidate region in affected and healthy family members as well as in control subjects. The results revealed allelic association between FMD and several individual polymorphic marker alleles and single-nucleotide polymorphisms. Moreover, a common three-marker haplotype spanning 1.48 Mb co-segregates with FMD in 60% of the families investigated, forming the core of a possible ancestral haplotype associated with FMD in Sweden.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Yamakawa, K. Pathologic changes in a Ménière's patient. Proc. 42nd Meet. Jpn. Otorhinolaryngol. Soc. 44, 2310–2312 (1938).
Hallpike, C. Observations on the pathology of Meniere's disease. J. Laryngol. Otol. 53, 625–654 (1938).
Wladislavosky-Waserman, P., Facerm, G. W., Mokri, B. & Kurland, L. T. Meniere's disease: a 30-year epidemiologic and clinical study in Rochester, Mn, 1951-1980. Laryngoscope 94, 1098–1102 (1984).
Watanabe, Y., Mizukoshi, K., Shojaku, H., Watanabe, I., Hinoki, M. & Kitahara, M. Epidemiological and clinical characteristics of Meniere's disease in Japan. Acta Otolaryngol. 519, 206–210 (1995).
Celestino, D. & Ralli, G. Incidence of Meniere's disease in Italy. Am. J. Otol. 12, 135–138 (1991).
Cawthorne, T. & Hewlett, A. B. Meniere's disease. Proc. R. Soc. Med. 47, 663–670 (1954).
Stahle, J., Stahle, C. & Arenberg, I. K. Incidence of Meniere's disease. Arch. Otolaryngol. 104, 99–102 (1978).
Birgerson, L., Gustavson, K. H. & Stahle, J. Familial Meniere's disease: a genetic investigation. Am. J. Otol. 8, 323–326 (1987).
Martini, A. Hereditary Meniere's disease: report of two families. Am. J. Otolaryngol. 3, 163–167 (1982).
Morrison, A. W. Anticipation in Meniere's disease. J. Laryngol. Otol. 109, 499–502 (1995).
Arweiler, D. J., Jahnke, K. & Grosse-Wilde, H. [Meniere disease as an autosome dominant hereditary disease]. Laryngorhinootologie 74, 512–515 (1995).
Morrison, A. W. Meniere's disease. J. R. Soc. Med. 74, 183–189 (1981).
Klockars, T. & Kentala, E. Inheritance of Meniere's disease in the Finnish population. Arch. Otolaryngol. Head Neck Surg. 133, 73–77 (2007).
Fung, K., Xie, Y., Hall, S. F., Lillicrap, D. P. & Taylor, S. A. Genetic basis of familial Meniere's disease. J. Otolaryngol. 31, 1–4 (2002).
Koyama, S., Mitsuishi, Y., Bibee, K., Watanabe, I. & Terasaki, P. I. HLA associations with Meniere's disease. Acta Otolaryngol. 113, 575–578 (1993).
Robertson, N. G., Lu, L., Heller, S., Merchant, S. N., Eavey, R. D., McKenna, M. et al. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nat. Genet. 20, 299–303 (1998).
Fransen, E., Verstreken, M., Verhagen, W. I., Wuyts, F. L., Huygen, P. L., D’Haese, P. et al. High prevalence of symptoms of Meniere's disease in three families with a mutation in the COCH gene. Hum. Mol. Genet. 8, 1425–1429 (1999).
Verstreken, M., Declau, F., Wuyts, F. L., D’Haese, P., Van Camp, G., Fransen, E. et al. Hereditary otovestibular dysfunction and Meniere's disease in a large Belgian family is caused by a missense mutation in the COCH gene. Otol. Neurotol. 22, 874–881 (2001).
Usami, S., Takahashi, K., Yuge, I., Ohtsuka, A., Namba, A., Abe, S. et al. Mutations in the COCH gene are a frequent cause of autosomal dominant progressive cochleo-vestibular dysfunction, but not of Meniere's disease. Eur. J. Hum. Genet. 11, 744–748 (2003).
Sanchez, E., Lopez-Escamez, J. A., Lopez-Nevot, M. A., Lopez-Nevot, A., Cortes, R. & Martin, J. Absence of COCH mutations in patients with Meniere disease. Eur. J. Hum. Genet. 12, 75–78 (2004).
Lynch, M., Cameron, T. L., Knight, M., Kwok, T. Y., Thomas, P., Forrest, S. M. et al. Structural and mutational analysis of antiquitin as a candidate gene for Meniere disease. Am. J. Med. Genet. 110, 397–399 (2002).
Mhatre, A. N., Jero, J., Chiappini, I., Bolasco, G., Barbara, M. & Lalwani, A. K. Aquaporin-2 expression in the mammalian cochlea and investigation of its role in Meniere's disease. Hear. Res. 170, 59–69 (2002).
Teggi, R., Lanzani, C., Zagato, L., Delli Carpini, S., Manunta, P., Bianchi, G. et al. Gly460Trp alpha-adducin mutation as a possible mechanism leading to endolymphatic hydrops in Meniere's syndrome. Otol. Neurotol. 29, 824–828 (2008).
Lopez-Escamez, J. A., Saenz-Lopez, P., Acosta, L., Moreno, A., Gazquez, I., Perez-Garrigues, H. et al. Association of a functional polymorphism of PTPN22 encoding a lymphoid protein phosphatase in bilateral Meniere's disease. Laryngoscope 120, 103–107 (2010).
Doi, K., Sato, T., Kuramasu, T., Hibino, H., Kitahara, T., Horii, A. et al. Meniere's disease is associated with single nucleotide polymorphisms in the human potassium channel genes, KCNE1 and KCNE3. ORL J. Otorhinolaryngol. Relat. Spec. 67, 289–293 (2005).
Vrabec, J. T., Liu, L., Li, B. & Leal, S. M. Sequence variants in host cell factor C1 are associated with Meniere's disease. Otol. Neurotol. 29, 561–566 (2008).
Campbell, C. A., Della Santina, C. C., Meyer, N. C., Smith, N. B., Myrie, O. A., Stone, E. M. et al. Polymorphisms in KCNE1 or KCNE3 are not associated with Meniere disease in the Caucasian population. Am. J. Med. Genet. A 152A, 67–74 (2010).
Klar, J., Frykholm, C., Friberg, U. & Dahl, N. A. Meniere's disease gene linked to chromosome 12p12.3. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 463–467 (2006).
Monsell, M. E., Balkany, A. T., Gates, A. G., Goldenberg, . R., Meyerhoff, L. W. & House, W. J. Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy in Meniere's disease. American Academy of Otolaryngology-Head and Neck Foundation, Inc. Otolaryngol. Head Neck Surg. 113, 181–185 (1995).
Reese, M. G., Eeckman, F. H., Kulp, D. & Haussler, D. Improved splice site detection in Genie. J. Comput. Biol. 4, 311–323 (1997).
Klar, J., Gedde-Dahl, JrT., Larsson, M., Pigg, M., Carlsson, B., Tentler, D. et al. Assignment of the locus for ichthyosis prematurity syndrome to chromosome 9q33.3-34.13. J. Med. Genet. 41, 208–212 (2004).
Spielman, R. S., McGinnis, R. E. & Ewens, W. J. Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am. J. Hum. Genet. 52, 506–516 (1993).
Hastbacka, J., de la Chapelle, A., Mahtani, M. M., Clines, G., Reeve-Daly, M. P., Daly, M. et al. The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping. Cell 78, 1073–1087 (1994).
Kalinec, F., Zhang, M., Urrutia, R. & Kalinec, G. Rho GTPases mediate the regulation of cochlear outer hair cell motility by acetylcholine. J. Biol. Chem. 275, 28000–28005 (2000).
Ali, G., Santos, R. L., John, P., Wambangco, M. A., Lee, K., Ahmad, W. et al. The mapping of DFNB62, a new locus for autosomal recessive non-syndromic hearing impairment, to chromosome 12p13.2-p11.23. Clin. Genet. 69, 429–433 (2006).
Weston, M. D. & Soukup, G. A. MicroRNAs sound off. Genome Med. 1, 59 (2009).
Weston, M. D., Pierce, M. L., Rocha-Sanchez, S., Beisel, K. W. & Soukup, G. A. MicroRNA gene expression in the mouse inner ear. Brain Res. 1111, 95–104 (2006).
Tsonis, P. A., Call, M. K., Grogg, M. W., Sartor, M. A., Taylor, R. R., Forge, A. et al. MicroRNAs and regeneration: Let-7 members as potential regulators of dedifferentiation in lens and inner ear hair cell regeneration of the adult newt. Biochem. Biophys. Res. Commun. 362, 940–945 (2007).
Swiderski, D. L., Gong, T. W. & Mustapha, M. Complexity and integration in the control of inner-ear development. Genome Biol. 8, 315 (2007).
Soukup, G. A., Fritzsch, B., Pierce, M. L., Weston, M. D., Jahan, I., McManus, M. T. et al. Residual microRNA expression dictates the extent of inner ear development in conditional Dicer knockout mice. Dev. Biol. 328, 328–341 (2009).
Soukup, G. A. Little but loud: small RNAs have a resounding affect on ear development. Brain Res. 1277, 104–114 (2009).
Sacheli, R., Nguyen, L., Borgs, L., Vandenbosch, R., Bodson, M., Lefebvre, P. et al. Expression patterns of miR-96, miR-182 and miR-183 in the development inner ear. Gene Expr. Patterns 9, 364–370 (2009).
Mencia, A., Modamio-Hoybjor, S., Redshaw, N., Morin, M., Mayo-Merino, F., Olavarrieta, L. et al. Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss. Nat. Genet. 41, 609–613 (2009).
Fritzsch, B., Beisel, K. W., Pauley, S. & Soukup, G. Molecular evolution of the vertebrate mechanosensory cell and ear. Int. J. Dev. Biol. 51, 663–678 (2007).
Friedman, L. M., Dror, A. A., Mor, E., Tenne, T., Toren, G., Satoh, T. et al. MicroRNAs are essential for development and function of inner ear hair cells in vertebrates. Proc. Natl Acad. Sci. USA 106, 7915–7920 (2009).
Friedman, L. M. & Avraham, K. B. MicroRNAs and epigenetic regulation in the mammalian inner ear: implications for deafness. Mamm. Genome 20, 581–603 (2009).
Lewis, M. A., Quint, E., Glazier, A. M., Fuchs, H., De Angelis, M. H., Langford, C. et al. An ENU-induced mutation of miR-96 associated with progressive hearing loss in mice. Nat. Genet. 41, 614–618 (2009).
Wallis, D., Hamblen, M., Zhou, Y., Venken, K. J., Schumacher, A., Grimes, H. L. et al. The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development 130, 221–232 (2003).
Goodyear, R. J., Legan, P. K., Wright, M. B., Marcotti, W., Oganesian, A., Coats, S. A. et al. A receptor-like inositol lipid phosphatase is required for the maturation of developing cochlear hair bundles. J. Neurosci. 23, 9208–9219 (2003).
Author information
Authors and Affiliations
Corresponding author
Additional information
Supplementary Information accompanies the paper on Journal of Human Genetics website
Supplementary information
Rights and permissions
About this article
Cite this article
Gabriková, D., Frykholm, C., Friberg, U. et al. Familiar Meniere's disease restricted to 1.48 Mb on chromosome 12p12.3 by allelic and haplotype association. J Hum Genet 55, 834–837 (2010). https://doi.org/10.1038/jhg.2010.122
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/jhg.2010.122
Keywords
This article is cited by
-
Genetic advances in Meniere Disease
Molecular Biology Reports (2023)
-
Variable expressivity and genetic heterogeneity involving DPT and SEMA3D genes in autosomal dominant familial Meniere’s disease
European Journal of Human Genetics (2017)
-
M. Menière: Diagnostische Kriterien des Internationalen Klassifikationskomitees der Bárány-Gesellschaft
HNO (2017)
