ORIGINAL ARTICLE
PREVALENCE OF DFNB1 HEARING LOSS AMONG COCHLEAR IMPLANT USERS ESTABLISHED WITH THE 3-STEP DFNB1 APPROACH
Agnieszka Pollak 1, A,C-G
,
 
 
 
 
More details
Hide details
1
Department of Genetics, Institute of Physiology and Pathology of Hearing, Warsaw/Kajetany, Poland
 
2
Oto-Rhino-Laryngology Surgery Clinic, Institute of Physiology and Pathology of Hearing, Warsaw/Kajetany, Poland
 
 
A - Research concept and design; B - Collection and/or assembly of data; C - Data analysis and interpretation; D - Writing the article; E - Critical revision of the article; F - Final approval of article;
 
 
Publication date: 2017-03-31
 
 
Corresponding author
Agnieszka Pollak   

Agnieszka Pollak, Department of Genetics, Institute of Physiology and Pathology of Hearing, Mokra 17 Str., Kajetany, 05-830, Nadarzyn, Poland, e-mail: a.pollak@ifps.org.pl
 
 
J Hear Sci 2017;7(1):33-40
 
KEYWORDS
ABSTRACT
Background:
Intensive studies have been conducted worldwide to elucidate the genetic basis of hearing impairment (HI). The aim of this study was to estimate the prevalence of DFNB1-related HI among patients with cochlear implants (CI).

Material and Methods:
We analyzed 1262 consecutive patients diagnosed with hearing loss who received a CI. At the time of writing this is the largest CI cohort tested for DFNB1 mutations. The search for mutations was done using our 3-step diagnostic approach to DFNB1 testing (3-step DFNB1 approach) comprising a range of molecular methods: multiplex PCR, PCR-RFLP, allele-specific PCR, Sanger sequencing, and real-time PCR with dedicated TaqMan probes.

Results:
Our results show that DFNB1 deafness is present in 39.3% of Polish CI recipients. The most commonly detected causative variant in the study group was c.35delG within the GJB2 gene. The majority of the revealed DFNB1 variants were truncating, and related to early HI onset as well as profound hearing loss.

Conclusions:
The data conclusively show that mutations in the DFNB1 locus are the main cause of HI among CI patients, and that the proposed 3-step DFNB1 approach is a fast, effective, and economical method for DFNB1 screening

 
REFERENCES (47)
1.
Parving A. Factors causing hearing impairment: Aome perspectives from Europe. J Am Acad Audiol, 1995, 6(5): 387–95.
 
2.
Nance WE: The genetics of deafness. Mental Retardation and Developmental Disabilities Research Reviews, 2003; 9(2): 109–19.
 
3.
Morton NE. Genetic epidemiology of hearing impairment. Ann N Acad Sci, 1991; 630: 16–31.
 
4.
Van Camp G, Willems PJ, Smith RJ. Nonsyndromic hearing impairment: Unparalleled heterogeneity. Am J Hum Genet, 1997; 60(4): 758–64.
 
5.
Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G et al: Connexin 26 mutations in hereditary non-syndromic sensorineural deafness. Nature, 1997; 387(6628): 80–83.
 
6.
Zelante L, Gasparini P, Estivill X, Melchionda S, D’Agruma L, Govea N et al. Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans. Hum Mol Genet, 1997; 6(9): 1605–9.
 
7.
Bargiello TA, Tang Q, Oh S, Kwon T: Voltage-dependent conformational changes in connexin channels. Biochim Biophys Acta, 2012; 1818(8): 1807–22.
 
8.
Nance WE, Kearsey MJ: Relevance of connexin deafness (DFNB1) to human evolution. Am J Hum Genet, 2004; 74(6): 1081–87.
 
9.
Van Laer L, Coucke P, Mueller RF, Caethoven G, Flothmann K, Prasad SD et al. A common founder for the 35delG GJB2 gene mutation in connexin 26 hearing impairment. J Med Genet, 2001; 38(8): 515–18.
 
10.
Gasparini P, Rabionet R, Barbujani G, Melchionda S, Petersen M, Brondum-Nielsen K et al. High carrier frequency of the 35delG deafness mutation in European populations. Genetic Analysis Consortium of GJB2 35delG. Eur J Hum Genet, 2000; 8(1): 19–23.
 
11.
Estivill X, Fortina P, Surrey S, Rabionet R, Melchionda S, D’Agruma L et al. Connexin-26 mutations in sporadic and inherited sensorineural deafness. Lancet, 1998; 351(9100): 394–98.
 
12.
Cohn ES, Kelley PM. Clinical phenotype and mutations in connexin 26 (DFNB1/GJB2), the most common cause of childhood hearing loss. Am J Med Genet, 1999; 89(3): 130–36.
 
13.
del Castillo I, Villamar M, Moreno-Pelayo MA, del Castillo FJ, Alvarez A, Telleria D et al. A deletion involving the connexin 30 gene in nonsyndromic hearing impairment. New Engl J Med, 2002; 346(4): 243–49.
 
14.
del Castillo FJ, Rodriguez-Ballesteros M, Alvarez A, Hutchin T, Leonardi E, de Oliveira CA et al. A novel deletion involving the connexin-30 gene, del(GJB6-d13s1854), found in trans with mutations in the GJB2 gene (connexin-26) in subjects with DFNB1 non-syndromic hearing impairment. J Med Genet, 2005; 42(7): 588–94.
 
15.
Del Castillo I, Moreno-Pelayo MA, Del Castillo FJ, Brownstein Z, Marlin S, Adina Q et al. Prevalence and evolutionary origins of the del(GJB6-D13S1830) mutation in the DFNB1 locus in hearing-impaired subjects: A multicenter study. Am J Hum Genet, 2003; 73(6): 1452–58.
 
16.
Lenarz T, Pau HW, Paasche G. Cochlear implants. Curr Pharm Biotechnol, 2013; 14(1): 112–23.
 
17.
Eshraghi AA, Nazarian R, Telischi FF, Rajguru SM, Truy E, Gupta C. The cochlear implant: historical aspects and future prospects. Anat Rec (Hoboken), 2012; 295(11): 1967–80.
 
18.
Skarzynski H, Janczewski G, Niemczyk K, Kochanek K, Geremek A, Klasek O. [First cochlear implant in Poland]. Otolaryngologia Polska [Polish Otolaryngology], 1993; 47(5): 427–34.
 
19.
Skarzynski H, Lorens A, Piotrowska A, Anderson I. Partial deafness cochlear implantation in children. Int J Pediatr Otorhinolaryngol, 2007; 71(9): 1407–13.
 
20.
Skarzynski H, Lorens A, Piotrowska A, Anderson I. Partial deafness cochlear implantation provides benefit to a new population of individuals with hearing loss. Acta Otolaryngol, 2006; 126(9): 934–40.
 
21.
Skarzynski H, Lorens A, Piotrowska A. A new method of partial deafness treatment. Med Sci Monit, 2003, 9(4): CS20–24.
 
22.
Skarzynski H, Lorens A, Dziendziel B, Skarzynski PH. Expanding pediatric cochlear implant candidacy: A case study of electro-natural stimulation (ENS) in partial deafness treatment. Int J Pediatric Otorhinolaryngol, 2015; 79(11): 1896–900.
 
23.
Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res, 1988, 16(3): 1215.
 
24.
Pollak A, Skorka A, Mueller-Malesinska M, Waligora J, Korniszewski L, Skarzynski H et al. Nowa metoda diagnostyki molekularnej niedosłuchu uwarunkowanego genetycznie. Audiofonologia, 2005; 27: 63–65. [in Polish].
 
25.
Pollak A: Connexins associated deafness: Spectrum of mutations and clinical phenotype among Polish patients. Warsaw Medical University; 2010.
 
26.
Kenneson A, Van Naarden Braun K, Boyle C. GJB2 (connexin 26) variants and nonsyndromic sensorineural hearing loss: A HuGE review. Genet Med, 2002; 4(4): 258–74.
 
27.
Kabahuma RI, Ouyang X, Du LL, Yan D, Hutchin T, Ramsay M et al. Absence of GJB2 gene mutations, the GJB6 deletion (GJB6-D13S1830) and four common mitochondrial mutations in nonsyndromic genetic hearing loss in a South African population. Int J Pediatr Otorhinolaryngol, 2011; 75(5): 611–17.
 
28.
Bhalla S, Sharma R, Khandelwal G, Panda NK, Khullar M. Low incidence of GJB2, GJB6 and mitochondrial DNA mutations in North Indian patients with non-syndromic hearing impairment. Biochem Biophys Res Commun, 2009; 385(3): 445–48.
 
29.
Yan D, Tekin D, Bademci G, Foster J 2nd, Cengiz FB, KannanSundhari A et al. Spectrum of DNA variants for non-syndromic deafness in a large cohort from multiple continents. Hum Genet, 2016; 135(8): 953–61.
 
30.
Propst EJ, Stockley TL, Gordon KA, Harrison RV, Papsin BC. Ethnicity and mutations in GJB2 (connexin 26) and GJB6 (connexin 30) in a multi-cultural Canadian paediatric cochlear implant program. Int J Pediatr Otorhinolaryngol, 2006; 70(3): 435–44.
 
31.
Mueller-Malesinska M, Nowak M, Skarzynski H, Ploski R, Waligora J, Korniszewski L. Epidemiology of 35delG mutation in GJB2 gene in a Polish population. Journal of Audiological Medicine, 2001; 10: 136–41.
 
32.
Pollak A, Skorka A, Mueller-Malesinska M, Kostrzewa G, Kisiel B, Waligora J et al. M34T and V37I mutations in GJB2 associated hearing impairment: Evidence for pathogenicity and reduced penetrance. Am J Med Genet A, 2007; 143A(21): 2534–43.
 
33.
Mueller-Malesinska M, Pollak A, Lechowicz U, Skorka A, Oldak M, Skarżyński H et al. 35delG mutation in patients with non-genetic risk factors for hearing impairment (NGRF-HI): an attempt to estimate NGRF-HI effect sizes. In: 1st Congress of the Confederation of the European ORL-HNS, Barcelona, Spain; 2011.
 
34.
Burke WF, Warnecke A, Schoner-Heinisch A, Lesinski-Schiedat A, Maier H, Lenarz T. Prevalence and audiological profiles of GJB2 mutations in a large collective of hearing impaired patients. Hear Res, 2016; 333: 77–86.
 
35.
Daneshi A, Hassanzadeh S, Emamdjomeh H, Mohammadi SH, Arzhangi S, Farhadi M, Najmabadi H. Prevalence of GJB2-associated deafness and outcomes of cochlear implantation in Iran. J Laryngol Otol, 2011; 125(5): 455–59.
 
36.
Wu CC, Liu TC, Wang SH, Hsu CJ, Wu CM. Genetic characteristics in children with cochlear implants and the corresponding auditory performance. Laryngoscope, 2011; 121(6): 1287–93.
 
37.
Varga L, Masindova I, Huckova M, Kabatova Z, Gasperikova D, Klimes I et al. Prevalence of DFNB1 mutations among cochlear implant users in Slovakia and its clinical implications. Eur Arch Otorhinolaryngol,2014; 271(6): 1401–7.
 
38.
Radulescu L, Martu C, Birkenhager R, Cozma S, Ungureanu L, Laszig R. Prevalence of mutations located at the dfnb1 locus in a population of cochlear implanted children in eastern Romania. Int J Pediatr Otorhinolaryngol, 2012; 76(1): 90–94.
 
39.
Chora JR, Matos TD, Martins JH, Alves MC, Andrade SM, Silva LF et al. DFNB1-associated deafness in Portuguese cochlear implant users: Prevalence and impact on oral outcome. Int J Pediatr Otorhinolaryngol, 2010; 74(10): 1135–39.
 
40.
Snoeckx RL, Huygen PL, Feldmann D, Marlin S, Denoyelle F, Waligora J et al. GJB2 mutations and degree of hearing loss: A multicenter study. Am J Hum Genet, 2005; 77(6): 945–57.
 
41.
Pollak A, Lechowicz U, Kedra A, Stawinski P, Rydzanicz M, Furmanek M et al. Novel and de novo mutations extend association of POU3F4 with distinct clinical and radiological phenotype of hearing loss. PLoS One, 2016, 11(12): e0166618.
 
42.
Vona B, Muller T, Nanda I, Neuner C, Hofrichter MA, Schroder J et al. Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations. Genet Med, 2014; 16(12): 945–53.
 
43.
Miyagawa M, Nishio SY, Usami S. A comprehensive study on the etiology of patients receiving cochlear implantation with special emphasis on genetic epidemiology. Otol Neurotol, 2016; 37(2): e126–34.
 
44.
Eppsteiner RW, Shearer AE, Hildebrand MS, Deluca AP, Ji H, Dunn CC et al. Prediction of cochlear implant performance by genetic mutation: The spiral ganglion hypothesis. Hear Res, 2012; 292(1–2): 51–58.
 
45.
Abdurehim Y, Lehmann A, Zeitouni AG. Predictive value of GJB2 mutation status for hearing outcomes of pediatric cochlear implantation. Otolaryngol Head Neck Surg, 2017 [Epub ahead of print].
 
46.
Lorens A, Polak M, Piotrowska A, Skarzynski H. Outcomes of treatment of partial deafness with cochlear implantation: A DUET study. Laryngoscope, 2008; 118(2): 288–94.
 
47.
Connell SS, Angeli SI, Suarez H, Hodges AV, Balkany TJ, Liu XZ. Performance after cochlear implantation in DFNB1 patients. Otolaryngol Head Neck Surg, 2007; 137(4): 596–602.
 
Journals System - logo
Scroll to top