Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-23T20:17:24.342Z Has data issue: false hasContentIssue false
  • English
  • Français

Bioinformatics analysis of candidate genes and mutations in a congenital sensorineural hearing loss pedigree: detection of 52 genes for the DFNA52 locus

Published online by Cambridge University Press:  29 February 2008

Pan Qiong ,
Z Hu ,
Y Feng ,
Q Pan ,
J Xia  and
K Xia
Pan Qiong
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China These authors contributed equally to this work
Z Hu
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China These authors contributed equally to this work
Y Feng*
Affiliation:
Department of Otorhinology, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
Q Pan
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
J Xia
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
K Xia*
Affiliation:
National Laboratory of Medical Genetics of China, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China
*
Address for correspondence: Dr Yong Feng, The Department of Otorhinology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan, China. Fax: +86 731 4327469 E-mail: [email protected]
Dr Kun Xia, Central South University, National Laboratory of Medical Genetics of China, 110 Xiangya Road, Changsha, Hunan, China. Fax: +86 731 4478152 E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Objective:

Previously, we have mapped the DFNA52 (Online Mendelian Inheritance in Man (OMIM) 607683) locus, using an 8.8-cM interval on the human chromosome 5q31.1-q32, in a large, consanguineous Chinese family with congenital sensorineural hearing loss. In order to identify the responsible pathogenic mutation within the DFNA52 locus, we set out to identify candidate disease genes within that region and to sequentially analyse these candidate genes.

Methods:

Using bioinformatics analysis, 52 candidate disease genes were identified based on gene expression data, deafness phenotype, and findings from a mouse model and from the literature (including two mouse deafness genes NEUROG1 and SMAD5). Mutation detection was performed for the 52 candidate genes, in patients from the pedigree.

Results:

In these patients, we found no disease-causing mutations in the coding and splice site regions of these genes, which segregated with the disease. However, 108 single nucleotide polymorphisms were identified, of which 15 were novel. Eleven of these 108 single nucleotide polymorphisms altered the encoded amino acid.

Conclusions:

Although we identified a number of nucleotide changes in the affected patients, by analysis of coding and splice site regions of the genes, none of these changes are likely to be pathogenic mutations segregating with the disease. The result implies that the genes studied are unlikely to be a cause of DFNA52-linked sensorineural hearing loss.

Keywords

Sensorineural DeafnessDFNA ProteinGenetic Diseases
Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 122 , Issue 10 , October 2008 , pp. 1029 - 1036
Copyright
Copyright © JLO (1984) Limited 2008

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Cohen, MM, Gorlin, RJ. Epidemiology, etiology and genetic patterns. In: Gorlin, RJ, Toriello, HV, Cohen, MM, Hereditary Hearing Loss and Its Syndromes. Oxford: Oxford University Press, 1995;43–61Google Scholar
2 Morton, NE. Genetic epidemiology of hearing impairment. Ann N Y Acad Sci 1991;630:16–31CrossRefGoogle ScholarPubMed
3 The Hereditary Hearing loss Homepage. http://webh01.ua.ac.be/hhh/ [July 16, 2006]Google Scholar
4 Xia, J, Deng, H, Feng, Y, Zhang, H, Pan, Q, Dai, H et al. A novel locus for autosomal dominant nonsyndromic hearing loss identified at 5q31.1-32 in a Chinese pedigree. J Hum Genet 2002;47:635–40CrossRefGoogle Scholar
5 Gurtler, N, Kim, Y, Mhatre, A, Schlegel, C, Mathis, A, Lalwani, AK et al. DFNA54, a third locus for low-frequency hearing loss. J Mol Med 2004;82:775–80CrossRefGoogle ScholarPubMed
6 Table of gene expression in the developing ear. http://www.ihr.mrc.ac.uk/legacy/hereditary/genetable [April 2002]Google Scholar
7 Resendes, BL, Robertson, NG, Szustakowski, JD, Resendes, RJ, Weng, Z, Morton, CC. Gene discovery in the auditory system: characterization of additional cochlear-expressed sequences. J Assoc Res Otolaryngol 2002;3:45–53CrossRefGoogle ScholarPubMed
8 Pompeia, C, Hurle, B, Belyantseva, IA, Noben-Trauth, K, Beisel, K, Gao, J et al. Gene expression profile of the mouse organ of Corti at the onset of hearing. Genomics 2004;83:1000–11CrossRefGoogle ScholarPubMed
9 Weil, D, Blanchard, S, Kaplan, J, Guilford, P, Gibson, F, Walsh, J et al. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature 1995;374:60–1CrossRefGoogle ScholarPubMed
10 Liu, XZ, Walsh, J, Mburu, P, Kendrick-Jones, J, Cope, MJ, Steel, KP et al. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet 1997;16:188–90CrossRefGoogle ScholarPubMed
11 Weil, D, Kussel, P, Blanchard, S, Levy, G, Levi-Acobas, F, Drira, M et al. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nat Genet 1997;16:191–3CrossRefGoogle ScholarPubMed
12 Liu, XZ, Walsh, J, Tamagawa, Y, Kitamura, K, Nishizawa, M, Steel, KP et al. Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene. Nat Genet 1997;17:268–9CrossRefGoogle ScholarPubMed
13 Wang, A, Liang, Y, Fridell, RA, Probst, FJ, Wilcox, ER, Touchman, JW et al. Association of unconventional myosin MYO15 mutations with human nonsyndromic deafness DFNB3. Science 1998;280:1447–51CrossRefGoogle ScholarPubMed
14 Vahava, O, Morell, R, Lynch, ED, Weiss, S, Kagan, ME, Ahituv, N et al. Mutation in transcription factor POU4F3 associated with inherited progressive hearing loss in humans. Science 1998;279:1950–4CrossRefGoogle ScholarPubMed
15 Ma, Q, Anderson, DJ, Fritzsch, B. Neurogenin 1 null mutant ears develop fewer, morphologically normal hair cells in smaller sensory epithelia devoid of innervation. J Assoc Res Otolaryngol 2000;1:129–43CrossRefGoogle ScholarPubMed
16 Guo, Wei, Yang, Shi-Ming, Liu, Qing-Ming, Sun, Yan-Xun, Yang, Xia, Han, Dong-Yi et al. The mutation in Smad5 genes lead to severe hearing loss in mouse. Chinese Journal of Otology 2006;4:190–3Google Scholar
17 Abe, S, Katagiri, T, Saito-Hisaminato, A, Usami, S, Inoue, Y, Tsunoda, T et al. Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues. Am J Hum Genet 2003;72:73–82CrossRefGoogle ScholarPubMed
18 Alsaber, R, Tabone, CJ, Kandpal, RP. Predicting candidate genes for human deafness disorders: a bioinformatics approach. BMC Genomics 2006;19:180CrossRefGoogle Scholar
19 Coucke, PJ, Van Hauwe, P, Kelley, PM, Kunst, H, Schatteman, I, Van Velzen, D et al. Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families. Hum Molec Genet 1999;8:1321–8CrossRefGoogle ScholarPubMed
20 Kubisch, C, Schroeder, BC, Friedrich, T, Lutjohann, B, El-Amraoui, A, Marlin, S et al. KCNQ4, a novel potassium channel expressed in sensory outer hair cells, is mutated in dominant deafness. Cell 1999;96:437–46CrossRefGoogle ScholarPubMed
21 Blader, P, Lam, CS, Rastegar, S, Scardigli, R, Nicod, JC, Simplicio, N et al. Conserved and acquired features of neurogenin1 regulation. Development 2004;131:5627–37CrossRefGoogle ScholarPubMed
22 Sun, Jian-He, Yang, Shi-Ming, Sun, Yan-Xun, Yang, Xiao, Han, Dong-Yi, Yang, Wei-Yan et al. Scanning electron microscopic morphology in the cochlea of Smad5 mutant mice. Chinese Journal of Otology 2006;4:194–6Google Scholar
23 Wang, Qiu-Ju, Li, Qing-Zhong, Zong, Liang, Guo, Wei, Lan, Lan, Yuan, Hu, Zhao, Ya-Li et al. Mutation screening of Smad5 gene in patients with hearing loss in China. Chinese Journal of Otology 2006;4:200–4Google Scholar
24 Li, XC, Everett, LA, Lalwani, AK, Desmukh, D, Friedman, TB, Green, ED et al. A mutation in PDS causes non-syndromic recessive deafness. Nat Genet 1998, 18:215–17CrossRefGoogle ScholarPubMed
25 Everett, LA, Glaser, B, Beck, JC, Idol, JR, Buchs, A, Heyman, M et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997;17:411–22CrossRefGoogle Scholar
26 Usami, S, Abe, S, Weston, MD, Shinkawa, H, Van Camp, G, Kimberling, WJ. Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations. Hum Genet 1999;104:188–92CrossRefGoogle ScholarPubMed
27 Park, HJ, Shaukat, S, Liu, XZ, Hahn, SH, Naz, S, Ghosh, M et al. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet 2003;40:242–8CrossRefGoogle Scholar
28 Bolz, H, von Brederlow, B, Ramirez, A, Bryda, EC, Kutsche, K, Nothwang, HG et al. Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D. Nat Genet 2001;27:108–12CrossRefGoogle ScholarPubMed
29 Bork, JM, Peters, LM, Riazuddin, S, Bernstein, SL, Ahmed, ZM, Ness, SL et al. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23. Am J Hum Genet 2001;68:26–37CrossRefGoogle ScholarPubMed
30 Ahmed, ZM, Riazuddin, S, Ahmad, J, Bernstein, SL, Guo, Y, Sabar, MF et al. 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 2003;12:3215–23CrossRefGoogle ScholarPubMed
31 Ahmed, ZM, Riazuddin, S, Bernstein, SL, Ahmed, Z, Khan, S, Griffith, AJ et al. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1F. Am J Hum Genet 2001;69:25–34CrossRefGoogle ScholarPubMed
32 Di Palma, F, Holme, RH, Bryda, EC, Belyantseva, IA, Pellegrino, R, Kachar, B et al. Mutations in Cdh23, encoding a new type of cadherin, cause stereocilia disorganization in Waltzer, the mouse model for Usher syndrome type 1D. Nat Genet 2001;27:103–7CrossRefGoogle ScholarPubMed
33 Alagramam, KN, Murcia, CL, Kwon, HY, Pawlowski, KS, Wright, CG, Woychik, RP. The mouse Ames Waltzer hearing-loss mutant is caused by mutation of Pcdh15, a novel protocadherin gene. Nat Genet 2001;27:99–102CrossRefGoogle ScholarPubMed