Accurate epidemiological data on common deafness genes are essential to improve the efficiency and to reduce the cost of molecular diagnosis. They may depend on several factors, including a clear delineation of the source of patients being studied. In the present study, we hypothesize that patients with idiopathic sensorineural hearing loss recruited from different sources might reveal discrepancies in the epidemiological results of genetic screening, because patients from different sources might demonstrate distinct clinical or audiologic features and thus result in biased selection of subjects. To elucidate the relative importance of common deafness genes in Taiwanese and to verify our hypothesis, we conducted a prospective project screening mutations in GJB2, SLC26A4 and mitochondrial 12S rRNA gene in a total of 420 Taiwanese families with idiopathic bilateral sensorineural hearing loss, of which 325 families were recruited from hospitals and 95 from hearing rehabilitation facilities. Allele frequencies of common mutations in these three genes and distributions of the corresponding genotypes were then compared between the two groups. The allele frequencies of mutations in SLC26A4, GJB2 and mitochondrial 12S rRNA in the probands of the 420 families were 14.4, 21.7 and 3.8%, respectively. The allele frequency of SLC26A4 mutations in the hospital group was significantly higher than that in the rehabilitation facility group (16.2 vs. 8.4%, χ2-test, p < 0.05), whereas no difference in the frequencies of GJB2 mutations and mitochondrial 12S rRNA mutations was found between the two groups. Distributions of probands classified by SLC26A4 genotypes were also different between the two groups (χ2-test, p < 0.05). Accordingly, a discrepancy in the genetic screening results might exist between different sources of idiopathic hearing-impaired patients. Further analysis of audiological results and construction of a logistic regression model showed that different audiological features, namely hearing levels and hearing loss patterns, might be responsible for the unequal distributions of mutations and probands between the hospital and rehabilitation facility groups.

Keywords:
GJB2, SLC26A4, Mitochondrial 12S rRNA, Genetic epidemiology, Idiopathic sensorineural hearing impairment
1.
Abe S, Usami S, Shinkawa H, Kelley PM, Kimberling WJ: Prevalent connexin 26 gene (GJB2) mutations in Japanese. J Med Genet 2000;37:41–43.
2.
Albert S, Blons H, Jonard L, Feldmann D, Chauvin P, Loundon N, Sergent-Allaoui A, Houang M, Joannard A, Schmerber S, Delobel B, Leman J, Journel H, Catros H, Dollfus H, Eliot MM, David A, Calais C, Drouin-Garraud V, Obstoy MF, Tran Ba Huy P, Lacombe D, Duriez F, Francannet C, Bitoun P, Petit C, Garabedian EN, Couderc R, Marlin S, Denoyelle F: SLC26A4 gene is frequently involved in nonsyndromic hearing impairment with enlarged vestibular aqueduct in Caucasian populations. Eur J Hum Genet 2006;14:773–779.
3.
Alvarez A, del Castillo I, Villamar M, Aguirre LA, Gonzalez-Neira A, Lopez-Nevot A, Moreno-Pelayo MA, Moreno F: High prevalence of the W24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss. Am J Med Genet A 2005;137:255–258.
4.
Antonelli PJ, Varela AE, Mancuso AA: Diagnostic yield of high-resolution computed tomography for pediatric sensorineural hearing loss. Laryngoscope 1999;109:1642– 1647.
5.
Belintani Piatto V, Maria Goloni Bertollo E, Lucia Sartorato E, Victor Maniglia J: Prevalence of the GJB2 mutations and the del(GJB6-D13S1830) mutation in Brazilian patients with deafness. Hear Res 2004;196:87–93.
6.
Blons H, Feldmann D, Duval V, Messaz O, Denoyelle F, Loundon N, Sergout-Allaoui A, Houang M, Duriez F, Lacombe D, Delobel B, Leman J, Catros H, Journel H, Drouin-Garraud V, Obstoy MF, Toutain A, Oden S, Toublanc JE, Couderc R, Petit C, Garabedian EN, Marlin S: Screening of SLC26A4 (PDS) gene in Pendred’s syndrome: a large spectrum of mutations in France and phenotypic heterogeneity. Clin Genet 2004;66:333–340.
7.
Campbell C, Cucci RA, Prasad S, Green GE, Edeal JB, Galer CE, Karniski LP, Sheffield VC, Smith RJ: Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat 2001;17:403–411.
8.
Coyle B, Reardon W, Herbrick JA, Tsui LC, Gausden E, Lee J, Coffey R, Grueters A, Grossman A, Phelps PD, Luxon L, Kendall-Taylor P, Scherer SW, Trembath RC: Molecular analysis of the PDS gene in Pendred syndrome. Hum Mol Genet 1998;7:1105–1112.
9.
Dalamon V, Beheran A, Diamante F, Pallares N, Diamante V, Elgoyhen AB: Prevalence of GJB2 mutations and the del(GJB6-D13S1830) in Argentinean non-syndromic deaf patients. Hear Res 2005;207:43–49.
10.
Denoyelle F, Weil D, Maw MA, Wilcox SA, Lench NJ, Allen-Powell DR, Osborn AH, Dahl HH, Middleton A, Houseman MJ, Dode C, Marlin S, Boulila-ElGaied A, Grati M, Ayadi H, BenArab S, Bitoun P, Lina-Granade G, Godet J, Mustapha M, Loiselet J, El-Zir E, Aubois A, Joannard A, Petit C, et al: Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene. Hum Mol Genet 1997;6:2173–2177.
11.
Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED: Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet 1997;17:411–422.
12.
Frei K, Szuhai K, Lucas T, Weipoltshammer K, Schofer C, Ramsebner R, Baumgartner WD, Raap AK, Bittner R, Wachtler FJ, Kirschhofer K: Connexin 26 mutations in cases of sensorineural deafness in eastern Austria. Eur J Hum Genet 2002;10:427–432.
13.
Gabriel H, Kupsch P, Sudendey J, Winterhager E, Jahnke K, Lautermann J: Mutations in the connexin26/GJB2 gene are the most common event in non-syndromic hearing loss among the German population. Hum Mutat 2001;17:521–522.
14.
Gazzaz B, Weil D, Rais L, Akhyat O, Azeddoug H, Nadifi S: Autosomal recessive and sporadic deafness in Morocco: high frequency of the 35delG GJB2 mutation and absence of the 342-kb GJB6 variant. Hear Res 2005;210:80–84.
15.
Green GE, Scott DA, McDonald JM, Woodworth GG, Sheffield VC, Smith RJ: Carrier rates in the midwestern United States for GJB2 mutations causing inherited deafness. JAMA 1999;281:2211–2216.
16.
Gurtler N, Kim Y, Mhatre A, Muller R, Probst R, Lalwani AK: GJB2 mutations in the Swiss hearing impaired. Ear Hear 2003;24:440–447.
17.
Hutchin TP, Thompson KR, Parker M, Newton V, Bitner-Glindzicz M, Mueller RF: Prevalence of mitochondrial DNA mutations in childhood/congenital onset non-syndromal sensorineural hearing impairment. J Med Genet 2001;38:229–231.
18.
Hwa HL, Ko TM, Hsu CJ, Huang CH, Chiang YL, Oong JL, Chen CC, Hsu CK: Mutation spectrum of the connexin 26 (GJB2) gene in Taiwanese patients with prelingual deafness. Genet Med 2003;5:161–165.
19.
Jackler RK, Luxford WM, House WF: Congenital malformations of the inner ear: a classification based on embryogenesis. Laryngoscope 1987;97:2–14.
20.
Kalay E, Caylan R, Kremer H, de Brouwer AP, Karaguzel A: GJB2 mutations in Turkish patients with ARNSHL: prevalence and two novel mutations. Hear Res 2005;203:88–93.
21.
Kimberling WJ: Estimation of the frequency of occult mutations for an autosomal recessive disease in the presence of genetic heterogeneity: application to genetic hearing loss disorders. Hum Mutat 2005;26:462–470.
22.
Lim LH, Bradshaw JK, Guo Y, Pilipenko V, Madden C, Ingala D, Keddache M, Choo DI, Wenstrup R, Greinwald JH Jr: Genotypic and phenotypic correlations of DFNB1-related hearing impairment in the Midwestern United States. Arch Otolaryngol Head Neck Surg 2003;129:836–840.
23.
Liu XZ, Xia XJ, Ke XM, Ouyang XM, Du LL, Liu YH, Angeli S, Telischi FF, Nance WE, Balkany T, Xu LR: The prevalence of connexin 26 (GJB2) mutations in the Chinese population. Hum Genet 2002;111:394–397.
24.
Mafong DD, Shin EJ, Lalwani AK: Use of laboratory evaluation and radiologic imaging in the diagnostic evaluation of children with sensorineural hearing loss. Laryngoscope 2002;112:1–7.
25.
Maheshwari M, Vijaya R, Ghosh M, Shastri S, Kabra M, Menon PS: Screening of families with autosomal recessive non-syndromic hearing impairment (ARNSHI) for mutations in GJB2 gene: Indian scenario. Am J Med Genet A 2003;120:180–184.
26.
Malik SG, Pieter N, Sudoyo H, Kadir A, Marzuki S: Prevalence of the mitochondrial DNA A1555G mutation in sensorineural deafness patients in island Southeast Asia. J Hum Genet 2003;48:480–483.
27.
Morell RJ, Kim HJ, Hood LJ, Goforth L, Friderici K, Fisher R, Van Camp G, Berlin CI, Oddoux C, Ostrer H, Keats B, Friedman TB: Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness. N Engl J Med 1998;339:1500–1505.
28.
Pandya A, Arnos KS, Xia XJ, Welch KO, Blanton SH, Friedman TB, Garcia Sanchez G, Liu MX, Morell R, Nance WE: Frequency and distribution of GJB2 (connexin 26) and GJB6 (connexin 30) mutations in a large North American repository of deaf probands. Genet Med 2003;5:295–303.
29.
Park HJ, Hahn SH, Chun YM, Park K, Kim HN: Connexin26 mutations associated with nonsyndromic hearing loss. Laryngoscope 2000;110:1535–1538.
30.
Park HJ, Lee SJ, Jin HS, Lee JO, Go SH, Jang HS, Moon SK, Lee SC, Chun YM, Lee HK, Choi JY, Jung SC, Griffith AJ, Koo SK: Genetic basis of hearing loss associated with enlarged vestibular aqueducts in Koreans. Clin Genet 2005;67:160–165.
31.
Park HJ, Shaukat S, Liu XZ, Hahn SH, Naz S, Ghosh M, Kim HN, Moon SK, Abe S, Tukamoto K, Riazuddin S, Kabra M, Erdenetungalag R, Radnaabazar J, Khan S, Pandya A, Usami SI, Nance WE, Wilcox ER, Riazuddin S, Griffith AJ: Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet 2003;40:242–248.
32.
Prasad S, Kolln KA, Cucci RA, Trembath RC, Van Camp G, Smith RJ: Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations. Am J Med Genet A 2004;124:1–9.
33.
Tsukamoto K, Suzuki H, Harada D, Namba A, Abe S, Usami S: Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese. Eur J Hum Genet 2003;11:916–922.
34.
Usami S, Abe S, Akita J, Namba A, Shinkawa H, Ishii M, Iwasaki S, Hoshino T, Ito J, Doi K, Kubo T, Nakagawa T, Komiyama S, Tono T, Komune S: Prevalence of mitochondrial gene mutations among hearing impaired patients. J Med Genet 2000;37:38–40.
35.
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;104:188–192.
36.
Wu CC, Chen PJ, Hsu CJ: Specificity of SLC26A4 mutations in the pathogenesis of inner ear malformations. Audiol Neurootol 2005a;10:234–242.
37.
Wu CC, Chen YS, Chen PJ, Hsu CJ: Common clinical features of children with enlarged vestibular aqueduct and Mondini dysplasia. Laryngoscope 2005b;115:132–137.
38.
Wu CC, Chiu YH, Chen PJ, Hsu CJ: Prevalence and clinical features of the mitochondrial m.1555A>G mutation in Taiwanese patients with idiopathic sensorineural hearing loss and association of haplogroup F with low penetrance in three families. Ear Hear 2007;28:332–342.
39.
Wu CC, Yeh TH, Chen PJ, Hsu CJ: Prevalent SLC26A4 mutations in patients with enlarged vestibular aqueduct and/or Mondini dysplasia: a unique spectrum of mutations in Taiwan, including a frequent founder mutation. Laryngoscope 2005c;115:1060–1064.
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