Limits...
Residual Hearing in DFNB1 Deafness and Its Clinical Implication in a Korean Population.

Kim SY, Kim AR, Han KH, Kim MY, Jeon EH, Koo JW, Oh SH, Choi BY - PLoS ONE (2015)

Bottom Line: Of the 130 subjects, 22 (16.9%) were found to carry at least one mutant allele of GJB2.The c.235delC mutation was shown to have the most common allele frequency (39.0%) among GJB2 mutations, followed by p.R143W (26.8%) and p.V37I (9.8%).The c.235delC mutation showed a particularly wide spectrum of hearing loss, from mild to profound and significantly better hearing thresholds at 250 Hz and 2k Hz than in the non-p.V37I and non-235delC nonsyndromic hearing loss and deafness 1(DFNB1) subjects.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT

Introduction: The contribution of Gap junction beta-2 protein (GJB2) to the genetic load of deafness and its mutation spectra vary among different ethnic groups.

Objective: In this study, the mutation spectrum and audiologic features of patients with GJB2 mutations were evaluated with a specific focus on residual hearing.

Methods: An initial cohort of 588 subjects from 304 families with varying degrees of hearing loss were collected at the otolaryngology clinics of Seoul National University Hospital and Seoul National University Bundang Hospital from September 2010 through January 2014. GJB2 sequencing was carried out for 130 probands with sporadic or autosomal recessive non syndromic hearing loss. The audiograms were evaluated in the GJB2 mutants.

Results: Of the 130 subjects, 22 (16.9%) were found to carry at least one mutant allele of GJB2. The c.235delC mutation was shown to have the most common allele frequency (39.0%) among GJB2 mutations, followed by p.R143W (26.8%) and p.V37I (9.8%). Among those probands without the p.V37I allele in a trans configuration who showed some degree of residual hearing, the mean air conduction thresholds at 250 and 500 Hz were 57 dB HL and 77.8 dB HL, respectively. The c.235delC mutation showed a particularly wide spectrum of hearing loss, from mild to profound and significantly better hearing thresholds at 250 Hz and 2k Hz than in the non-p.V37I and non-235delC nonsyndromic hearing loss and deafness 1(DFNB1) subjects.

Conclusion: Despite its reputation as the cause of severe to profound deafness, c.235delC, the most frequent DFNB1 mutation in our cohort, caused a wide range of hearing loss with some residual hearing in low frequencies. This finding can be of paramount help for prediction of low frequency hearing thresholds in very young DFNB1 patients and highlights the importance of soft surgery for cochlear implantation in these patients.

No MeSH data available.


Related in: MedlinePlus

Overlapping audiograms of the patients with c.235delC and non-c.235delC GJB2 mutations.A. Patients with hearing loss caused by a c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 13). B. Patients with hearing loss caused by a non-c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 5). Detailed lists of non-c.235delC mutations are p.R143W homozygote, p.R143W single heterozygote, p.Glu47* and p.Ala171Glufs*40 compound heterozygote, and p.T86R and p.R143W compound heterozygote. (*p = 0.05, **p = 0.03, by the Mann-Whitney U test) (Black dots mean hearing thresholds of each subject, which may represent more than one subject with identical hearing thresholds. Red dots represent mean hearing thresholds of each frequency).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4464755&req=5

pone.0125416.g003: Overlapping audiograms of the patients with c.235delC and non-c.235delC GJB2 mutations.A. Patients with hearing loss caused by a c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 13). B. Patients with hearing loss caused by a non-c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 5). Detailed lists of non-c.235delC mutations are p.R143W homozygote, p.R143W single heterozygote, p.Glu47* and p.Ala171Glufs*40 compound heterozygote, and p.T86R and p.R143W compound heterozygote. (*p = 0.05, **p = 0.03, by the Mann-Whitney U test) (Black dots mean hearing thresholds of each subject, which may represent more than one subject with identical hearing thresholds. Red dots represent mean hearing thresholds of each frequency).

Mentions: The non-p.V37I DFNB1 subjects (n = 18) exhibited a mean hearing threshold of 93.5 dB (Fig 2), again confirming GJB2 mutations as an important cause of pre-lingual severe to profound SNHL in this Korean cohort. Notably, they retained some degree of residual hearing, leading to hearing thresholds of 57 dB HL and 82.9 dB HL at 250 and 500 Hz, respectively. This audiogram configuration is different from the relatively flat audiogram over all frequencies for the p.V37I DFNB1 subjects (Fig 2). Breaking down the hearing results according to genotype, the most frequent GJB2 mutation in the non-p.V37I DFNB1 subjects, c.235delC, caught our attention due to the wide range of hearing thresholds and relatively good residual hearing—especially at low frequencies (Fig 3). Although the variance between the non-p.V37I groups with and without c.235delC was not significantly different due to the small sample number, the non-p.V37I group with c.235delC subjects demonstrated a wide range of hearing thresholds. Notably, two c.235delC homozygotes (SH 111–230 and SB 128–220) showed dramatically different levels of hearing loss (Fig 4). When we compared the hearing thresholds of all measured frequencies and width of the hearing threshold ranges of the non-p.V37I DFNB1 subjects carrying c.235delC with those of non-p.V37I and non-c.235delC DFNB1 subjects, those DFNB1 subjects who carried c.235delC showed a significantly better hearing threshold than did the non-p.V37I and non-c.235delC DFNB1 subjects at 250 Hz and 2 kHz, respectively (p = 0.05, 0.03, Mann-Whitney U test) (Fig 3).


Residual Hearing in DFNB1 Deafness and Its Clinical Implication in a Korean Population.

Kim SY, Kim AR, Han KH, Kim MY, Jeon EH, Koo JW, Oh SH, Choi BY - PLoS ONE (2015)

Overlapping audiograms of the patients with c.235delC and non-c.235delC GJB2 mutations.A. Patients with hearing loss caused by a c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 13). B. Patients with hearing loss caused by a non-c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 5). Detailed lists of non-c.235delC mutations are p.R143W homozygote, p.R143W single heterozygote, p.Glu47* and p.Ala171Glufs*40 compound heterozygote, and p.T86R and p.R143W compound heterozygote. (*p = 0.05, **p = 0.03, by the Mann-Whitney U test) (Black dots mean hearing thresholds of each subject, which may represent more than one subject with identical hearing thresholds. Red dots represent mean hearing thresholds of each frequency).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4464755&req=5

pone.0125416.g003: Overlapping audiograms of the patients with c.235delC and non-c.235delC GJB2 mutations.A. Patients with hearing loss caused by a c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 13). B. Patients with hearing loss caused by a non-c.235delC mutation (excluding patients with a p.V37I mutation in the trans configuration) (n = 5). Detailed lists of non-c.235delC mutations are p.R143W homozygote, p.R143W single heterozygote, p.Glu47* and p.Ala171Glufs*40 compound heterozygote, and p.T86R and p.R143W compound heterozygote. (*p = 0.05, **p = 0.03, by the Mann-Whitney U test) (Black dots mean hearing thresholds of each subject, which may represent more than one subject with identical hearing thresholds. Red dots represent mean hearing thresholds of each frequency).
Mentions: The non-p.V37I DFNB1 subjects (n = 18) exhibited a mean hearing threshold of 93.5 dB (Fig 2), again confirming GJB2 mutations as an important cause of pre-lingual severe to profound SNHL in this Korean cohort. Notably, they retained some degree of residual hearing, leading to hearing thresholds of 57 dB HL and 82.9 dB HL at 250 and 500 Hz, respectively. This audiogram configuration is different from the relatively flat audiogram over all frequencies for the p.V37I DFNB1 subjects (Fig 2). Breaking down the hearing results according to genotype, the most frequent GJB2 mutation in the non-p.V37I DFNB1 subjects, c.235delC, caught our attention due to the wide range of hearing thresholds and relatively good residual hearing—especially at low frequencies (Fig 3). Although the variance between the non-p.V37I groups with and without c.235delC was not significantly different due to the small sample number, the non-p.V37I group with c.235delC subjects demonstrated a wide range of hearing thresholds. Notably, two c.235delC homozygotes (SH 111–230 and SB 128–220) showed dramatically different levels of hearing loss (Fig 4). When we compared the hearing thresholds of all measured frequencies and width of the hearing threshold ranges of the non-p.V37I DFNB1 subjects carrying c.235delC with those of non-p.V37I and non-c.235delC DFNB1 subjects, those DFNB1 subjects who carried c.235delC showed a significantly better hearing threshold than did the non-p.V37I and non-c.235delC DFNB1 subjects at 250 Hz and 2 kHz, respectively (p = 0.05, 0.03, Mann-Whitney U test) (Fig 3).

Bottom Line: Of the 130 subjects, 22 (16.9%) were found to carry at least one mutant allele of GJB2.The c.235delC mutation was shown to have the most common allele frequency (39.0%) among GJB2 mutations, followed by p.R143W (26.8%) and p.V37I (9.8%).The c.235delC mutation showed a particularly wide spectrum of hearing loss, from mild to profound and significantly better hearing thresholds at 250 Hz and 2k Hz than in the non-p.V37I and non-235delC nonsyndromic hearing loss and deafness 1(DFNB1) subjects.

View Article: PubMed Central - PubMed

Affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.

ABSTRACT

Introduction: The contribution of Gap junction beta-2 protein (GJB2) to the genetic load of deafness and its mutation spectra vary among different ethnic groups.

Objective: In this study, the mutation spectrum and audiologic features of patients with GJB2 mutations were evaluated with a specific focus on residual hearing.

Methods: An initial cohort of 588 subjects from 304 families with varying degrees of hearing loss were collected at the otolaryngology clinics of Seoul National University Hospital and Seoul National University Bundang Hospital from September 2010 through January 2014. GJB2 sequencing was carried out for 130 probands with sporadic or autosomal recessive non syndromic hearing loss. The audiograms were evaluated in the GJB2 mutants.

Results: Of the 130 subjects, 22 (16.9%) were found to carry at least one mutant allele of GJB2. The c.235delC mutation was shown to have the most common allele frequency (39.0%) among GJB2 mutations, followed by p.R143W (26.8%) and p.V37I (9.8%). Among those probands without the p.V37I allele in a trans configuration who showed some degree of residual hearing, the mean air conduction thresholds at 250 and 500 Hz were 57 dB HL and 77.8 dB HL, respectively. The c.235delC mutation showed a particularly wide spectrum of hearing loss, from mild to profound and significantly better hearing thresholds at 250 Hz and 2k Hz than in the non-p.V37I and non-235delC nonsyndromic hearing loss and deafness 1(DFNB1) subjects.

Conclusion: Despite its reputation as the cause of severe to profound deafness, c.235delC, the most frequent DFNB1 mutation in our cohort, caused a wide range of hearing loss with some residual hearing in low frequencies. This finding can be of paramount help for prediction of low frequency hearing thresholds in very young DFNB1 patients and highlights the importance of soft surgery for cochlear implantation in these patients.

No MeSH data available.


Related in: MedlinePlus