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DFNB48, a new nonsyndromic recessive deafness locus, maps to chromosome 15q23-q25.1

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Nonsyndromic deafness locus (DFNB48) segregating as an autosomal recessive trait has been mapped to the long arm of chromosome 15 in bands q23-q25.1 in five large Pakistani families. The deafness phenotype in one of these five families (PKDF245) is linked to D15S1005 with a lod score of 8.6 at θ=0, and there is a critical linkage interval of approximately 7 cM on the Marshfield human genetic map, bounded by microsatellite markers D15S216 (70.73 cM) and D15S1041 (77.69 cM). MYO9A, NR2E3, BBS4, and TMC3 are among the candidate genes in the DFNB48 region. The identification of another novel nonsyndromic recessive deafness locus demonstrates the high degree of locus heterogeneity for hearing impairment, particularly in the Pakistani population.

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  1. Ahmed ZM, Morell RJ, Riazuddin S, Gropman A, Shaukat S, Ahmad MM, Mohiddin SA, Fananapazir L, Caruso RC, Husnain T, Khan SN, Riazuddin S, Griffith AJ, Friedman TB, Wilcox ER (2003a) Mutations of MYO6 are associated with recessive deafness, DFNB37. Am J Hum Genet 72:1315–1322

  2. Ahmed ZM, Riazuddin S, Riazuddin S, Wilcox ER (2003b) The molecular genetics of Usher syndrome. Clin Genet 63:431–444

  3. Berg JS, Powell BC, Cheney RE (2001) A millennial myosin census. Mol Biol Cell 12:780–794

  4. Campbell DA, McHale DP, Brown KA, Moynihan LM, Houseman M, Karbani G, Parry G, Janiva AH, Newton V, Al-Gazali L, Markham AF, Lecch NJ, Mueller RF (1997) A new locus for non-syndromic, autosomal recessive, sensorineural hearing loss (DFNB16) maps to human chromosome 15q21-q22. J Med Genet 34:1015–1017

  5. Donaudy F, Ferrara A, Esposito L, Hertzano R, Ben-David O, Bell RE, Melchionda S, Zelante L, Avraham KB, Gasparini P (2003) Multiple mutations of MYO1A, a cochlear-expressed gene, in sensorineural hearing loss. Am J Hum Genet 72:1571–1577

  6. Donaudy F, Snoeckx R, Pfister M, Zenner H, Blin N, Di Stazio M, Ferrara A, Lanzara C, Ficarella R, Declau F, Pusch CM, Nürnberg P, Melchionda S, Zelante L, Ballana E, Estivill X, Camp GV, Gasparini P, Savoia A (2004) Nonmuscle myosin heavy-chain gene MYH14 is expressed in cochlea and mutated in patients affected by autosomal dominant hearing impairment (DFNA4). Am J Hum Genet 74:770–776

  7. Friedman TB, Griffith AJ (2003) Human nonsyndromic sensorineural deafness. Annu Rev Genomics Hum Genet 4:341–402

  8. Gibson F, Walsh J, Mburu P, Varela A, Brown KA, Antonio M, Beisel KW, Steel KP, Brown SD (1995) A type VII myosin encoded by the mouse deafness gene shaker-1. Nature 374:62–64

  9. Gorman SW, Haider NB, Grieshammer U, Swiderski RE, Kim E, Welch JW, Searby C, Leng S, Carmi R, Sheffield VC, Duhl DM (1999) The cloning and developmental expression of unconventional myosin IXA (MYO9A) a gene in the Bardet-Biedl syndrome (BBS4) region at chromosome 15q22-q23. Genomics 59:150–160

  10. Grimberg J, Nawoschik L, Belluscio R, Mckee A, Turck A, Eisenberg A (1989) A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res 17:8390

  11. Haider NB, Jacobson SG, Cideciyan AV, Swiderski R, Streb LM, Searby C, Beck G, Hockey R, Hanna DB, Gorman S, Duhl D, Carmi R, Bennett J, Weleber RG, Fishman GA, Wright AF, Stone EM, Sheffield VC (2000) Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate. Nat Genet 24:127–131

  12. Hussain R, Bittles AH (1998) The prevalence and demographic characteristics of consanguineous marriages in Pakistan. J Biosoc Sci 30:261–275

  13. Kobayashi M, Takezawa S-I, Hara K, Yu RT, Umesono Y, Agata K, Taniwaki M, Yasuda K, Ymesono K (1999) Identification of a photoreceptor cell-specific nuclear receptor. Proc Natl Acad Sci USA 96:4814–4819

  14. Kurima K, Peters LM, Yang YD, Riazuddin S, Ahmed ZM, Naz S, Arnaud D, Drury S, Mo JH, Makishima T, Ghosh M, Menon PSN, Deshmukh D, Oddoux C, Ostrer H, Khan S, Riazuddin S, Deininger PL, Hampton LL, Sullivan SL, Battey JF, Keats BJB, Wilcox ER, Friedman TB, Griffith AJ (2002) Dominant and recessive deafness caused by mutations of a novel gene, TMC1, required for cochlear hair-cell function. Nat Genet 30:277–284

  15. Kurima K, Yang YD, Sorber K, Griffith AJ (2003) Characterization of the transmembrane channel-like (TMC) gene family: functional clues from hearing loss and epidermodysplasia verruciformis. Genomics 82:300–308

  16. Lalwani AK, Goldstein JA, Kelley MJ, Luxford W, Castelein CM, Mhatre AN (2000) Human nonsyndromic hereditary deafness DFNA17 is due to a mutation in nonmuscle myosin MYH9. Am J Hum Genet 67:1121–1128

  17. Liburd N, Ghosh M, Riazuddin S, Naz S, Khan S, Ahmed Z, Liang Y, Menon PS, Smith T, Smith AC, Chen KS, Lupski JR, Wilcox ER, Potocki L, Friedman TB (2001) Novel mutations of MYO15A associated with profound deafness in consanguineous families and moderately severe hearing loss in a patient with Smith-Magenis syndrome. Hum Genet 109:535–554

  18. Liu XZ, Walsh J, Mburu P, Kendrick-Jones J, Cope MJ, Steel KP, Brown SD (1997a) Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet 16:188–190

  19. Liu XZ, Walsh J, Tamagawa Y, Kitamura K, Nishizawa M, Steel KP, Brown SD (1997b) Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene. Nat Genet 17:268–269

  20. Mangino M, Flex E, Capon F, Sangiuolo F, Carraro E, Gualandi F, Mazzoli M, Martini A, Novelli G, Dallapiccola B (2001) Mapping of a new autosomal dominant nonsyndromic hearing loss locus (DFNA30) to chromosome 15q25-26. Eur J Hum Genet 9:667–671

  21. Melchionda S, Ahituv N, Bisceglia L, Sobe T, Glaser F, Rabionet R, Arbones ML, Notarangelo A, Di Iorio E, Carella M, Zelante L, Estivill X, Avraham KB, Gasparini P (2001) MYO6, the human homologue of the gene responsible for deafness in Snell’s waltzer mice, is mutated in autosomal dominant nonsyndromic hearing loss. Am J Hum Genet 69:635–640

  22. Mykytyn K, Braun T, Carmi R, Haider NB, Searsby CC, Shastri M, Beck G, Wright AF, Iannoaccone A, Elbedour K, Riise R, Baldi A, Raas-Rothschild A, Gorman SW, Duhl DM, Jacobson SG, Casavant T, Stone EM, Sheffield VC (2001) Identification of the gene that, when mutated, causes the human obesity syndrome BBS4. Nat Genet 28:188–191

  23. Povey S, Lovering R, Bruford E, Wright M, Lush M, Wain H (2001) The HUGO Gene Nomenclature Committee (HGNC). Hum Genet 109:678–680

  24. Probst FJ, Fridell RA, Raphael Y, Saunders TL, Wang A, Liang Y, Morell RJ, Touchman JW, Lyons RH, Noben-Trauth K, Friedman TB, Camper SA (1998) Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science 280:1444–1447

  25. Resendes BL, Williamson RE, Morton CC (2001) At the speed of sound: gene discovery in the auditory system. Am J Hum Genet 69:923–935

  26. Schaffer AA (1996) Faster linkage analysis computations for pedigrees with loops or unused alleles. Hum Hered 46:226–235

  27. Verpy E, Masmoudi S, Zwaenepoel I, Leibovici M, Hutchin TP, Castillo ID, Nouaille S, Blanchard S, Laine S, Popot JL, Moreno F, Muller RF, Petit C (2001) Mutations in a new gene encoding a protein of the hair bundle cause nonsyndromic deafness at the DFNB16 locus. Nature Genet 29:345–349

  28. Vreugde S, Ereven A, Kros CJ, Marcotti W, Fuchs H, Kurima K, Wilcox ER, Friedman TB, Griffith AJ, Balling R, Angelis MH de, Avraham KB, Steel KP (2002) Beethoven, a mouse model for dominant, progressive hearing loss DFNA36. Nat Genet 30:257–258

  29. Walsh T, Walsh V, Vreugde S, Hertzano R, Shahin H, Haika S, Lee MK, Kanaan M, King MC, Avraham KB (2002) From flies’ eyes to our ears: mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30. Proc Natl Acad Sci USA 99:7518–7523

  30. Wang A, Liang Y, Fridell RA, Probst FJ, Wilcox ER, Touchman JW, Morton CC, Morell RJ, Noben-Trauth K, Camper SA, Friedman TB (1998) Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science 280:1447–1451

  31. Weil D, Blanchard S, Kaplan J, Guilford P, Gibson F, Walsh J, Mburu P, Varela A, Levilliers J, Weston MD, Kelley PM, Kimberling WJ, Wagenaar M, Levi-Acobas F, Larget-Plet D, Munnich A, Steel KP, Brown SDM, Petit C (1995) Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature 374:60–61

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We are grateful to the families for their participation in this study. We thank Dennis Drayna, Robert Morell, Julie Schultz, and Rehan S. Shaikh for their comments on this manuscript. We also thank Sabiha Nazli and Farooq Sabar for their technical assistance. This study was supported by the Higher Education Commission, Islamabad, Pakistan, and by the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy, under project CRP/PAK02-01 (contract no. 02/013). The part of this study conducted in the USA was supported by intramural funds from the National Institute on Deafness and Other Communication Disorders (ZO1 DC000035-07 and Z01 DC000039-07).

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Correspondence to Sheikh Riazuddin.

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Ahmad, J., Khan, S.N., Khan, S.Y. et al. DFNB48, a new nonsyndromic recessive deafness locus, maps to chromosome 15q23-q25.1. Hum Genet 116, 407–412 (2005).

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  • Hearing Loss
  • Autosomal Recessive Trait
  • Pakistani Family
  • Nuclear Receptor Subfamily
  • Nonsyndromic Deafness