Hearing Screening Combined with Target Gene Panel Testing Increased Etiological Diagnostic Yield in Deaf Children

Abstract

Genetic testing is the gold standard for exploring the etiology of congenital hearing loss. Here, we enrolled 137 Chinese patients with congenital hearing loss to describe the molecular epidemiology by using 127 gene panel testing or 159 variant testing. Sixty-three deaf children received 127 gene panel testing, while seventy-four patients received 159 variant testing. By use of 127 gene panel testing, more mutant genes and variants were identified. The most frequent mutant genes were GJB2, SLC26A4, MYO15A, CDH23, and OTOF. By analyzing the patients who received 127 gene panel testing, we found that 51 deaf children carried variants which were not included in 159 variant testing. Therefore, a large number of patients would be misdiagnosed if only 159 variant testing is used. This study highlights the advantage of 127 gene panel testing, and it suggests that broader genetic testing should be done to identify the genetic etiology of congenital hearing loss.

Identification of four novel variants in the CDH23 gene from four affected families with hearing loss

“…In this study, we performed exome sequencing analysis for 351 affected individuals with hearing loss. Among the identified causal genes, variants in GJB2 and SLC26A4 were most frequently identified in this cohort, which is similar to previous reports ( Fu et al, 2019 ; Xie et al, 2021 ). Here, we reported the identification of four novel variants in the CDH23 gene ( Table 1 ), which significantly expanded the mutation spectrum of CDH23 -associated non-syndromic autosomal recessive deafness.…”

Identification of four novel variants in the CDH23 gene from four affected families with hearing loss

“…In this study, we performed exome sequencing analysis for 351 affected individuals with hearing loss. Among the identified causal genes, variants in GJB2 and SLC26A4 were most frequently identified in this cohort, which is similar to previous reports ( Fu et al, 2019 ; Xie et al, 2021 ). Here, we reported the identification of four novel variants in the CDH23 gene ( Table 1 ), which significantly expanded the mutation spectrum of CDH23 -associated non-syndromic autosomal recessive deafness.…”

Audiological Phenotype, Natural History, and Intervention in Chinese Patients With Auditory Neuropathy Caused by OTOF Variants

“…We upgraded its pathogenicity and categorized it as likely pathogenic (likely pathogenic = PM2 + PM3_Strong + PP3), and the identification of this locus in patients can be followed in the future. According to previous studies, the most frequent variant in OTOF is c.5816G>A (p.R1939Q), which has been detected in Japanese ( Matsunaga et al 2012 ; Iwasa et al 2013 , 2019 , 2022 ), Korean ( Chang et al 2015 ; Kim et al 2018 ), Chinese ( Xie et al 2021 ), and American ( Varga et al 2003 ) populations. This variant is considered to be a common pathogenic variant of AN in the Japanese and Korean populations, and it was also detected in this study (3/108).…”

Novel GJB2 mutation c.188delT compound with c.235delC causing non-syndromic hearing loss in a Chinese family: A case report

“…It can expand the screening scope and significantly enhance the detection rate of deafness genes. [ 22 , 23 ]…”

“…It can expand the screening scope and significantly enhance the detection rate of deafness genes. [22,23] The treatment of congenital deafness typically requires a multidisciplinary approach, which includes early intervention strategies like hearing aids, or cochlear implantation. [24] This procedure has transformed the management of severe to profound sensorineural hearing loss, offering individuals with deafness the opportunity for sound perception and the development of spoken language skills.…”

Identification of four novel variants in the CDH23 gene from four affected families with hearing loss

“…In this study, we performed exome sequencing analysis for 351 affected individuals with hearing loss. Among the identified causal genes, variants in GJB2 and SLC26A4 were most frequently identified in this cohort, which is similar to previous reports ( Fu et al, 2019 ; Xie et al, 2021 ). Here, we reported the identification of four novel variants in the CDH23 gene ( Table 1 ), which significantly expanded the mutation spectrum of CDH23 -associated non-syndromic autosomal recessive deafness.…”

Audiological Phenotype, Natural History, and Intervention in Chinese Patients With Auditory Neuropathy Caused by OTOF Variants

“…We upgraded its pathogenicity and categorized it as likely pathogenic (likely pathogenic = PM2 + PM3_Strong + PP3), and the identification of this locus in patients can be followed in the future. According to previous studies, the most frequent variant in OTOF is c.5816G>A (p.R1939Q), which has been detected in Japanese ( Matsunaga et al 2012 ; Iwasa et al 2013 , 2019 , 2022 ), Korean ( Chang et al 2015 ; Kim et al 2018 ), Chinese ( Xie et al 2021 ), and American ( Varga et al 2003 ) populations. This variant is considered to be a common pathogenic variant of AN in the Japanese and Korean populations, and it was also detected in this study (3/108).…”

Novel GJB2 mutation c.188delT compound with c.235delC causing non-syndromic hearing loss in a Chinese family: A case report

“…It can expand the screening scope and significantly enhance the detection rate of deafness genes. [ 22 , 23 ]…”

“…It can expand the screening scope and significantly enhance the detection rate of deafness genes. [22,23] The treatment of congenital deafness typically requires a multidisciplinary approach, which includes early intervention strategies like hearing aids, or cochlear implantation. [24] This procedure has transformed the management of severe to profound sensorineural hearing loss, offering individuals with deafness the opportunity for sound perception and the development of spoken language skills.…”

Identification of four novel variants in the CDH23 gene from four affected families with hearing loss

“…In this study, we performed exome sequencing analysis for 351 affected individuals with hearing loss. Among the identified causal genes, variants in GJB2 and SLC26A4 were most frequently identified in this cohort, which is similar to previous reports ( Fu et al, 2019 ; Xie et al, 2021 ). Here, we reported the identification of four novel variants in the CDH23 gene ( Table 1 ), which significantly expanded the mutation spectrum of CDH23 -associated non-syndromic autosomal recessive deafness.…”

Audiological Phenotype, Natural History, and Intervention in Chinese Patients With Auditory Neuropathy Caused by OTOF Variants

“…We upgraded its pathogenicity and categorized it as likely pathogenic (likely pathogenic = PM2 + PM3_Strong + PP3), and the identification of this locus in patients can be followed in the future. According to previous studies, the most frequent variant in OTOF is c.5816G>A (p.R1939Q), which has been detected in Japanese ( Matsunaga et al 2012 ; Iwasa et al 2013 , 2019 , 2022 ), Korean ( Chang et al 2015 ; Kim et al 2018 ), Chinese ( Xie et al 2021 ), and American ( Varga et al 2003 ) populations. This variant is considered to be a common pathogenic variant of AN in the Japanese and Korean populations, and it was also detected in this study (3/108).…”

Novel GJB2 mutation c.188delT compound with c.235delC causing non-syndromic hearing loss in a Chinese family: A case report

“…It can expand the screening scope and significantly enhance the detection rate of deafness genes. [ 22 , 23 ]…”

“…It can expand the screening scope and significantly enhance the detection rate of deafness genes. [22,23] The treatment of congenital deafness typically requires a multidisciplinary approach, which includes early intervention strategies like hearing aids, or cochlear implantation. [24] This procedure has transformed the management of severe to profound sensorineural hearing loss, offering individuals with deafness the opportunity for sound perception and the development of spoken language skills.…”