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Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population

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ABSTRACT

Discriminating between inherited and non-inherited sporadic hearing loss is challenging. Here, we attempted to delineate genetic inheritance in simplex cases of severe-to-profound congenital hearing loss in Korean children. Variations in SLC26A4 and GJB2 in 28 children with bilateral severe-to-profound non-syndromic hearing loss (NSHL) without familial history were analyzed using Sanger sequencing. Genetic analysis of individuals without mutations in SLC26A4 and GJB2 was performed by whole exome sequencing (WES). Bi-allelic mutations in SLC26A4 and GJB2 were identified in 12 and 3 subjects, respectively. Of the 13 individuals without mutations in SLC26A4 and GJB2, 2 and 1 carried compound heterozygous mutations in MYO15A and CDH23, respectively. Thus, 64.3% (18/28) of individuals with NSHL were determined to be genetically predisposed. Individuals with sporadic severe-to-profound NSHL were found to mostly exhibit an autosomal recessive inheritance pattern. Novel causative candidate genes for NSHL were identified by analysis of WES data of 10 families without mutations in known causative genes. Bi-allelic mutations predisposing to NSHL were identified in 64.3% of subjects with sporadic severe-to-profound NSHL. Given that several causative genes for NSHL are still unidentified, genetic inheritance of sporadic congenital hearing loss could be more common than that indicated by our results.

No MeSH data available.


Audiological performance of cochlear implantation.Twenty-five children received cochlear implants. They were sub-divided into three groups—the SLC26A4 mutation, other gene mutations (including GJB2, MYO15A, and CDH23), and unidentified etiology groups—according to genotype. (a) Preoperative hearing thresholds for auditory steady-state response (ASSR). (b) Comparison of preoperative categories of auditory performance (CAP) scores among the three groups. (c) Comparison of postoperative CAP scores among the three groups. (d) Comparison of improvement in age equivalence in terms of receptive and expressive language among the three groups. ns, not significant (one-way analysis of variance).
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f2: Audiological performance of cochlear implantation.Twenty-five children received cochlear implants. They were sub-divided into three groups—the SLC26A4 mutation, other gene mutations (including GJB2, MYO15A, and CDH23), and unidentified etiology groups—according to genotype. (a) Preoperative hearing thresholds for auditory steady-state response (ASSR). (b) Comparison of preoperative categories of auditory performance (CAP) scores among the three groups. (c) Comparison of postoperative CAP scores among the three groups. (d) Comparison of improvement in age equivalence in terms of receptive and expressive language among the three groups. ns, not significant (one-way analysis of variance).

Mentions: Of the 28 subjects included in the present study, 25 received cochlear implants for hearing rehabilitation. The mean age at operation was 26.0 ± 15.8 months. The type of implanted device was CI24RE (CochlearTM, Australia) or Concerto (Med-ElTM, Austria), depending on the decision of the patients. These 25 subjects were subdivided into three groups—the SLC26A4 mutation, other gene mutations (including GJB2, MYO15A, and CDH23), and unidentified etiology groups—according to genotype, and preoperative hearing thresholds for ASSR were compared among these groups (Fig. 2a). Although the group of individuals with mutations in other genes appeared to exhibit comparatively worse hearing thresholds at 500 and 1000 Hz, there were no significant differences in preoperative threshold among the three groups at any of the frequencies (two-way analysis of variance; P > 0.05). All three groups exhibited average preoperative CAP scores <2, where a score of 2 indicated response to spoken signals (e.g., “go” or “boo”). There were no statistically differences in the average preoperative or 6-month postoperative CAP scores among the groups (Fig. 2b and c)21. Age equivalence in terms of receptive and expressive language was evaluated according to the SELSI22. As shown in Fig. 2d, there were no significant differences in the improvement of receptive or expressive language among the groups.


Genetic Predisposition to Sporadic Congenital Hearing Loss in a Pediatric Population
Audiological performance of cochlear implantation.Twenty-five children received cochlear implants. They were sub-divided into three groups—the SLC26A4 mutation, other gene mutations (including GJB2, MYO15A, and CDH23), and unidentified etiology groups—according to genotype. (a) Preoperative hearing thresholds for auditory steady-state response (ASSR). (b) Comparison of preoperative categories of auditory performance (CAP) scores among the three groups. (c) Comparison of postoperative CAP scores among the three groups. (d) Comparison of improvement in age equivalence in terms of receptive and expressive language among the three groups. ns, not significant (one-way analysis of variance).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5382691&req=5

f2: Audiological performance of cochlear implantation.Twenty-five children received cochlear implants. They were sub-divided into three groups—the SLC26A4 mutation, other gene mutations (including GJB2, MYO15A, and CDH23), and unidentified etiology groups—according to genotype. (a) Preoperative hearing thresholds for auditory steady-state response (ASSR). (b) Comparison of preoperative categories of auditory performance (CAP) scores among the three groups. (c) Comparison of postoperative CAP scores among the three groups. (d) Comparison of improvement in age equivalence in terms of receptive and expressive language among the three groups. ns, not significant (one-way analysis of variance).
Mentions: Of the 28 subjects included in the present study, 25 received cochlear implants for hearing rehabilitation. The mean age at operation was 26.0 ± 15.8 months. The type of implanted device was CI24RE (CochlearTM, Australia) or Concerto (Med-ElTM, Austria), depending on the decision of the patients. These 25 subjects were subdivided into three groups—the SLC26A4 mutation, other gene mutations (including GJB2, MYO15A, and CDH23), and unidentified etiology groups—according to genotype, and preoperative hearing thresholds for ASSR were compared among these groups (Fig. 2a). Although the group of individuals with mutations in other genes appeared to exhibit comparatively worse hearing thresholds at 500 and 1000 Hz, there were no significant differences in preoperative threshold among the three groups at any of the frequencies (two-way analysis of variance; P > 0.05). All three groups exhibited average preoperative CAP scores <2, where a score of 2 indicated response to spoken signals (e.g., “go” or “boo”). There were no statistically differences in the average preoperative or 6-month postoperative CAP scores among the groups (Fig. 2b and c)21. Age equivalence in terms of receptive and expressive language was evaluated according to the SELSI22. As shown in Fig. 2d, there were no significant differences in the improvement of receptive or expressive language among the groups.

View Article: PubMed Central - PubMed

ABSTRACT

Discriminating between inherited and non-inherited sporadic hearing loss is challenging. Here, we attempted to delineate genetic inheritance in simplex cases of severe-to-profound congenital hearing loss in Korean children. Variations in SLC26A4 and GJB2 in 28 children with bilateral severe-to-profound non-syndromic hearing loss (NSHL) without familial history were analyzed using Sanger sequencing. Genetic analysis of individuals without mutations in SLC26A4 and GJB2 was performed by whole exome sequencing (WES). Bi-allelic mutations in SLC26A4 and GJB2 were identified in 12 and 3 subjects, respectively. Of the 13 individuals without mutations in SLC26A4 and GJB2, 2 and 1 carried compound heterozygous mutations in MYO15A and CDH23, respectively. Thus, 64.3% (18/28) of individuals with NSHL were determined to be genetically predisposed. Individuals with sporadic severe-to-profound NSHL were found to mostly exhibit an autosomal recessive inheritance pattern. Novel causative candidate genes for NSHL were identified by analysis of WES data of 10 families without mutations in known causative genes. Bi-allelic mutations predisposing to NSHL were identified in 64.3% of subjects with sporadic severe-to-profound NSHL. Given that several causative genes for NSHL are still unidentified, genetic inheritance of sporadic congenital hearing loss could be more common than that indicated by our results.

No MeSH data available.