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. 1999 Jul;36(7):532–536.

A gene for autosomal dominant hearing impairment (DFNA14) maps to a region on chromosome 4p16.3 that does not overlap the DFNA6 locus

G Van Camp 1, H Kunst 1, K Flothmann 1, W McGuirt 1, J Wauters 1, H Marres 1, M Verstreken 1, I Bespalova 1, M Burmeister 1, P H Van de Heyning 1, R Smith 1, P Willems 1, C Cremers 1, M Lesperance 1
PMCID: PMC1734405  PMID: 10424813

Abstract

Non-syndromic hearing impairment is one of the most heterogeneous hereditary conditions, with more than 40 reported gene localisations. We have identified a large Dutch family with autosomal dominant non-syndromic sensorineural hearing impairment. In most patients, the onset of hearing impairment is in the first or second decade of life, with a slow decline in the following decades, which stops short of profound deafness. The hearing loss is bilateral, symmetrical, and only affects low and mid frequencies up to 2000 Hz. In view of the phenotypic similarities of this family with an American family that has been linked to chromosome 4p16.3 (DFNA6), we investigated linkage to the DFNA6 region. Lod score calculations confirmed linkage to this region with two point lod scores above 6. However, as haplotype analysis indicated that the genetic defect in this family is located in a 5.6 cM candidate region that does not overlap the DFNA6 region, the new locus has been named DFNA14.


Keywords: non-syndromic hearing impairment; genetic linkage analysis; DFNA6; DFNA14

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Selected References

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  1. Allitto B. A., MacDonald M. E., Bucan M., Richards J., Romano D., Whaley W. L., Falcone B., Ianazzi J., Wexler N. S., Wasmuth J. J. Increased recombination adjacent to the Huntington disease-linked D4S10 marker. Genomics. 1991 Jan;9(1):104–112. doi: 10.1016/0888-7543(91)90226-5. [DOI] [PubMed] [Google Scholar]
  2. Chaïb H., Lina-Granade G., Guilford P., Plauchu H., Levilliers J., Morgon A., Petit C. A gene responsible for a dominant form of neurosensory non-syndromic deafness maps to the NSRD1 recessive deafness gene interval. Hum Mol Genet. 1994 Dec;3(12):2219–2222. doi: 10.1093/hmg/3.12.2219. [DOI] [PubMed] [Google Scholar]
  3. Coucke P., Van Camp G., Djoyodiharjo B., Smith S. D., Frants R. R., Padberg G. W., Darby J. K., Huizing E. H., Cremers C. W., Kimberling W. J. Linkage of autosomal dominant hearing loss to the short arm of chromosome 1 in two families. N Engl J Med. 1994 Aug 18;331(7):425–431. doi: 10.1056/NEJM199408183310702. [DOI] [PubMed] [Google Scholar]
  4. Dib C., Fauré S., Fizames C., Samson D., Drouot N., Vignal A., Millasseau P., Marc S., Hazan J., Seboun E. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. doi: 10.1038/380152a0. [DOI] [PubMed] [Google Scholar]
  5. Fagerheim T., Nilssen O., Raeymaekers P., Brox V., Moum T., Elverland H. H., Teig E., Omland H. H., Fostad G. K., Tranebjaerg L. Identification of a new locus for autosomal dominant non-syndromic hearing impairment (DFNA7) in a large Norwegian family. Hum Mol Genet. 1996 Aug;5(8):1187–1191. doi: 10.1093/hmg/5.8.1187. [DOI] [PubMed] [Google Scholar]
  6. Goldstein D. B., Ruiz Linares A., Cavalli-Sforza L. L., Feldman M. W. Genetic absolute dating based on microsatellites and the origin of modern humans. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6723–6727. doi: 10.1073/pnas.92.15.6723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jain P. K., Fukushima K., Deshmukh D., Ramesh A., Thomas E., Lalwani A. K., Kumar S., Plopis B., Skarka H., Srisailapathy C. R. A human recessive neurosensory nonsyndromic hearing impairment locus is potential homologue of murine deafness (dn) locus. Hum Mol Genet. 1995 Dec;4(12):2391–2394. doi: 10.1093/hmg/4.12.2391. [DOI] [PubMed] [Google Scholar]
  8. Kirschhofer K., Kenyon J. B., Hoover D. M., Franz P., Weipoltshammer K., Wachtler F., Kimberling W. J. Autosomal-dominant, prelingual, nonprogressive sensorineural hearing loss: localization of the gene (DFNA8) to chromosome 11q by linkage in an Austrian family. Cytogenet Cell Genet. 1998;82(1-2):126–130. doi: 10.1159/000015086. [DOI] [PubMed] [Google Scholar]
  9. Lathrop G. M., Lalouel J. M. Easy calculations of lod scores and genetic risks on small computers. Am J Hum Genet. 1984 Mar;36(2):460–465. [PMC free article] [PubMed] [Google Scholar]
  10. Leon P. E., Raventos H., Lynch E., Morrow J., King M. C. The gene for an inherited form of deafness maps to chromosome 5q31. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5181–5184. doi: 10.1073/pnas.89.11.5181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lesperance M. M., Hall J. W., 3rd, Bess F. H., Fukushima K., Jain P. K., Ploplis B., San Agustin T. B., Skarka H., Smith R. J., Wills M. A gene for autosomal dominant nonsyndromic hereditary hearing impairment maps to 4p16.3. Hum Mol Genet. 1995 Oct;4(10):1967–1972. doi: 10.1093/hmg/4.10.1967. [DOI] [PubMed] [Google Scholar]
  12. Manolis E. N., Yandavi N., Nadol J. B., Jr, Eavey R. D., McKenna M., Rosenbaum S., Khetarpal U., Halpin C., Merchant S. N., Duyk G. M. A gene for non-syndromic autosomal dominant progressive postlingual sensorineural hearing loss maps to chromosome 14q12-13. Hum Mol Genet. 1996 Jul;5(7):1047–1050. doi: 10.1093/hmg/5.7.1047. [DOI] [PubMed] [Google Scholar]
  13. Mochizuki T., Lemmink H. H., Mariyama M., Antignac C., Gubler M. C., Pirson Y., Verellen-Dumoulin C., Chan B., Schröder C. H., Smeets H. J. Identification of mutations in the alpha 3(IV) and alpha 4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet. 1994 Sep;8(1):77–81. doi: 10.1038/ng0994-77. [DOI] [PubMed] [Google Scholar]
  14. Prezant T. R., Agapian J. V., Bohlman M. C., Bu X., Oztas S., Qiu W. Q., Arnos K. S., Cortopassi G. A., Jaber L., Rotter J. I. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nat Genet. 1993 Jul;4(3):289–294. doi: 10.1038/ng0793-289. [DOI] [PubMed] [Google Scholar]
  15. Reid F. M., Vernham G. A., Jacobs H. T. A novel mitochondrial point mutation in a maternal pedigree with sensorineural deafness. Hum Mutat. 1994;3(3):243–247. doi: 10.1002/humu.1380030311. [DOI] [PubMed] [Google Scholar]
  16. Scott D. A., Carmi R., Elbedour K., Yosefsberg S., Stone E. M., Sheffield V. C. An autosomal recessive nonsyndromic-hearing-loss locus identified by DNA pooling using two inbred Bedouin kindreds. Am J Hum Genet. 1996 Aug;59(2):385–391. [PMC free article] [PubMed] [Google Scholar]
  17. Van Camp G., Willems P. J., Smith R. J. Nonsyndromic hearing impairment: unparalleled heterogeneity. Am J Hum Genet. 1997 Apr;60(4):758–764. [PMC free article] [PubMed] [Google Scholar]
  18. Verhoeven K., Van Laer L., Kirschhofer K., Legan P. K., Hughes D. C., Schatteman I., Verstreken M., Van Hauwe P., Coucke P., Chen A. Mutations in the human alpha-tectorin gene cause autosomal dominant non-syndromic hearing impairment. Nat Genet. 1998 May;19(1):60–62. doi: 10.1038/ng0598-60. [DOI] [PubMed] [Google Scholar]
  19. de Kok Y. J., Vossenaar E. R., Cremers C. W., Dahl N., Laporte J., Hu L. J., Lacombe D., Fischel-Ghodsian N., Friedman R. A., Parnes L. S. Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4. Hum Mol Genet. 1996 Sep;5(9):1229–1235. doi: 10.1093/hmg/5.9.1229. [DOI] [PubMed] [Google Scholar]
  20. van Camp G., Coucke P., Balemans W., van Velzen D., van de Bilt C., van Laer L., Smith R. J., Fukushima K., Padberg G. W., Frants R. R. Localization of a gene for non-syndromic hearing loss (DFNA5) to chromosome 7p15. Hum Mol Genet. 1995 Nov;4(11):2159–2163. doi: 10.1093/hmg/4.11.2159. [DOI] [PubMed] [Google Scholar]

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