Abstract
We ascertained three consanguineous Pakistani families (PKDF291, PKDF335 and PKDF793) segregating nonsyndromic recessive hearing loss. The hearing loss segregating in PKDF335 and PKDF793 is moderate to severe, whereas it is profound in PKDF291. The maximum two-point LOD scores are 3.01 (D19S1034), 3.85 (D19S894) and 3.71 (D19S894) for PKDF291, PKDF335 and PKDF793, respectively. Haplotype analyses of the three families define a 1.16 Mb region of overlap of the homozygous linkage intervals bounded by markers D19S216 (20.01 cM) and D19S1034 (20.75 cM). These results define a novel locus, DFNB72, on chromosome 19p13.3. There are at least 22 genes in the 1.16 Mb interval, including PTPRS, ZNRF4 and CAPS. We identified no pathogenic variants in the exons and flanking intronic sequences of these three genes in affected members of the DFNB72 families. DFNB72 is telomeric to DFNB68, the only other known deafness locus with statistically significant support for linkage to chromosome 19p.
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References
Ahmed ZM, Riazuddin S, Bernstein SL, Ahmed Z, Khan S, Griffith AJ, Morell RJ, Friedman TB, Riazuddin S, Wilcox ER (2001) Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet 69:25–34
Ahmed ZM, Riazuddin S, Ahmad J, Bernstein SL, Guo Y, Sabar MF, Sieving P, Riazuddin S, Griffith AJ, Friedman TB, Belyantseva IA, Wilcox ER (2003) PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23. Hum Mol Genet 12:3215–3223
Alagramam KN, Murcia CL, Kwon HY, Pawlowski KS, Wright CG, Woychik RP (2001a) The mouse Ames waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene. Nat Genet 27:99–102
Alagramam KN, Yuan H, Kuehn MH, Murcia CL, Wayne S, Srisailpathy CR, Lowry RB, Knaus R, Van Laer L, Bernier FP, Schwartz S, Lee C, Morton CC, Mullins RF, Ramesh A, Van Camp G, Hageman GS, Woychik RP, Genotype/Phenotype Correlation Smith RJ, Hagemen GS (2001b) Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. Hum Mol Genet 10:1709–1718
Bolz H, von Brederlow B, Ramirez A, Bryda EC, Kutsche K, Nothwang HG, Seeliger M, del C-Salcedo Cabrera M, Vila MC, Molina OP, Gal A, Kubisch C (2001) Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nat Genet 27:108–112
Bork JM, Peters M, Riazuddin S, Bernstein SL, Ahmed ZM (2001) Usher syndrome1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet 68:26–37
Chen A, Wayne S, Bell A, Ramesh A, Srisailapathy CR, Scott DA, Sheffield VC, Van Hauwe P, Zbar RI, Ashley J, Lovett M, Van Camp G, Smith RJ (1997) New gene for autosomal recessive non-syndromic hearing loss maps to either chromosome 3q or 19p. Am J Med Genet 71:467–471
Chen AH, Stephan DA, Hasson T, Fukushima K, Nelissen CM, Chen AF, Jun AI, Ramesh A, Van Camp G, Smith RJH (2001) MYO1F as a candidate gene for nonsyndromic deafness, DFNB15. Arch Otolaryngol Head Neck Surg 127:921–925
Chen W, Kahrizi K, Meyer NC, Riazalhosseini Y, Van Camp G, Najmabadi H, Smith RJ (2005) Mutation of COL11A2 causes autosomal recessive non-syndromic hearing loss at the DFNB53 locus. J Med Genet 42:e61
del Castillo I, Villamar M, Moreno-Pelayo MA, del Castillo FJ, Alvarez A, Telleria D, Menendez I, Moreno F (2002) A deletion involving the connexin 30 gene in nonsyndromic hearing impairment. N Engl J Med 346:243–249
Di Palma F, Holme RH, Bryda EC, Belyantseva IA, Pellegrino R, Kachar B, Steel KP, Noben-Trauth K (2001) Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in waltzer, the mouse model for Usher syndrome type 1D. Nat Genet 27:103–107
Eisen MD, Ryugo DK (2007) Hearing molecules: contributions from genetic deafness. Cell Mol Life Sci 64:566–580
Friedman TB, Griffith AJ (2003) Human nonsyndromic sensorineural deafness. Annu Rev Genomics Hum Genet 4:341–402
Friedman TB, Liang Y, Weber JL, Hinnant JT, Barber TD, Winata S, Arhya IN, Asher JH Jr (1995) A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17. Nat Genet 9:86–91
Goodyear RJ, Legan PK, Wright MB, Marcotti W, Oganesian A, Coats SA, Booth CJ, Kros CJ, Seifert RA, Bowen-Pope DF, Richardson GP (2003) A receptor-like inositol lipid phosphatase is required for the maturation of developing cochlear hair bundles. J Neurosci 23:9208–9219
Grimberg J, Nawoschik S, Belluscio L, McKee R, 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
Hastbacka J, de la Chapelle A, Kaitila I, Sistonen P, Weaver A, Lander E (1992) Linkage disequilibrium mapping in isolated founder populations: diastrophic dysplasia in Finland. Nat Genet 2:204–211
Lander ES, Botstein D (1987) Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children. Science 236:1567–1570
Lefort A, Lecocq R, Libert F, Lamy F, Swillens S, Vassart G, Dumont JE (1989) Cloning and sequencing of a calcium-binding protein regulated by cyclic AMP in the thyroid. EMBO J 8:111–116
Mburu P, Mustapha M, Varela A, Weil D, El-Amraoui A, Holme RH, Rump A, Hardisty RE, Blanchard S, Coimbra RS, Perfettini I, Parkinson N, Mallon AM, Glenister P, Rogers MJ, Paige AJ, Moir L, Clay J, Rosenthal A, Liu XZ, Blanco G, Steel KP, Petit C, Brown SD (2003) Defects in whirlin, a PDZ domain molecule involved in stereocilia elongation, cause deafness in the whirler mouse and families with DFNB31. Nat Genet 34:421–428
Morton CC, Nance WE (2006) Newborn hearing screening-a silent revolution. N Engl J Med 18:2151–2164
Naz S, Alasti F, Mowjoodi A, Riazuddin S, Sanati MH, Friedman TB, Griffith AJ, Wilcox ER, Riazuddin S (2003) Distinctive audiometric profile associated with DFNB21 alleles of TECTA. J Med Genet 40:360–363
Riazuddin S, Khan SN, Ahmed ZM, Ghosh M, Caution K, Nazli S, Kabra M, Zafar AU, Chen K, Naz S, Antonellis A, Pavan WJ, Green ED, Wilcox ER, Friedman PL, Morell RJ, Riazuddin S, Friedman TB (2006a) Mutations in TRIOBP, which encodes a putative cytoskeletal-organizing protein, are associated with nonsyndromic recessive deafness. Am J Hum Genet 78:137–143
Riazuddin S, Ahmed ZM, Fanning AS, Lagziel A, Kitajiri S, Ramzan K, Khan SN, Chattaraj P, Friedman PL, Anderson JM, Belyantseva IA, Forge A, Riazuddin S, Friedman TB (2006b) Tricellulin is a tight-junction protein necessary for hearing. Am J Hum Genet 79:1040–1051
Santos RL, Hassan MJ, Sikandar S, Lee K, Ali G, Martin PE Jr, Wambangco MA, Ahmad W, Leal SM (2006) DFNB68, a novel autosomal recessive non-syndromic hearing impairment locus at chromosomal region 19p13.2. Hum Genet 120:85–92
Schaffer AA (1996) Faster linkage analysis computations for pedigrees with loops or unused alleles. Hum Hered 46:226–235
Shabbir MI, Ahmed ZM, Khan SY, Riazuddin S, Waryah AM, Khan SN, Camps RD, Ghosh M, Kabra M, Belyantseva IA, Friedman TB, Riazuddin S (2006) Mutations of human TMHS cause recessively inherited non-syndromic hearing loss. J Med Genet 43:634–640
Shahin H, Walsh T, Sobe T, Abu Sa’ed J, Abu Rayan A, Lynch ED, Lee MK, Avraham KB, King MC, Kanaan M (2006) Mutations in a novel isoform of TRIOBP that encodes a filamentous-actin binding protein are responsible for DFNB28 recessive nonsyndromic hearing loss. Am J Hum Genet 78:144–152
Tlili A, Mannikko M, Charfedine I, Lahmar I, Benzina Z, Ben Amor M, Driss N, Ala-Kokko L, Drira M, Masmoudi S, Ayadi H (2005) A novel autosomal recessive non-syndromic deafness locus, DFNB66, maps to chromosome 6p21.2–22.3 in a large Tunisian consanguineous family. Hum Hered 60:123–128
Verpy E, Masmoudi S, Zwaenepoel I, Leibovici M, Hutchin TP, Del Castillo I, Nouaille S, Blanchard S, Lainé S, Popot JL, Moreno F, Mueller RF, Petit C (2001) Mutations in a new gene encoding a protein of the hair bundle cause non-syndromic deafness at the DFNB16 locus. Nat Genet 29:345–349
Wagner J, Gordon LA, Heng HHQ, Tremblay ML, Olsen AS (1996) Physical mapping of receptor type protein tyrosine phosphatase sigma (PTPRS) to human chromosome 19p13.3. Genomics 38:76–78
Wallis D, Hamblen M, Zhou Y, Venken KJ, Schumacher A, Grimes HL, Zoghbi HY, Orkin SH, Bellen HJ (2003) The zinc finger transcription factor Gfi1, implicated in lymphomagenesis, is required for inner ear hair cell differentiation and survival. Development 130:221–232
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
Zwaenepoel I, Mustapha M, Leibovici M, Verpy E, Goodyear R, Liu XZ, Nouaille S, Nance WE, Kanaan M, Avraham KB, Tekaia F, Loiselet J, Lathrop M, Richardson G, Petit C (2002) Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22. Proc Natl Acad Sci USA 99:6240–6245
Acknowledgments
The authors are grateful to the family members who participated in this research project and to Karen Friderici and Dennis Drayna for their comments and suggestions. This study was supported by the Higher Education Commission (HEC), Islamabad, Pakistan; EMRO/WHO-COMSTECH and Ministry of Science and Technology (MoST), Islamabad, Pakistan. Part of this study was supported by intramural funds (1 Z01 DC000064-06, 1 ZO1 DC000035-09 and 1 ZO1 DC000039-09) from the National Institute on Deafness and Other Communication Disorders, National Institutes of Health.
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Ain, Q., Nazli, S., Riazuddin, S. et al. The autosomal recessive nonsyndromic deafness locus DFNB72 is located on chromosome 19p13.3. Hum Genet 122, 445–450 (2007). https://doi.org/10.1007/s00439-007-0418-z
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DOI: https://doi.org/10.1007/s00439-007-0418-z