Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38

The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Hedwig M. Velde [verfasserIn] Xanne J. J. Huizenga [verfasserIn] Helger G. Yntema [verfasserIn] Lonneke Haer-Wigman [verfasserIn] Andy J. Beynon [verfasserIn] Jaap Oostrik [verfasserIn] Sjoert A. H. Pegge [verfasserIn] Hannie Kremer [verfasserIn] Cris P. Lanting [verfasserIn] Ronald J. E. Pennings [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	hereditary hearing loss DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss

Übergeordnetes Werk:	In: Genes - MDPI AG, 2010, 14(2023), 2, p 457
Übergeordnetes Werk:	volume:14 ; year:2023 ; number:2, p 457

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/genes14020457

Katalog-ID:	DOAJ080282474

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allfields	10.3390/genes14020457 doi (DE-627)DOAJ080282474 (DE-599)DOAJ2dc7721b383843beb3f210caf5cd5229 DE-627 ger DE-627 rakwb eng QH426-470 Hedwig M. Velde verfasserin aut Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods. hereditary hearing loss <i<WFS1</i< DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss Genetics Xanne J. J. Huizenga verfasserin aut Helger G. Yntema verfasserin aut Lonneke Haer-Wigman verfasserin aut Andy J. Beynon verfasserin aut Jaap Oostrik verfasserin aut Sjoert A. H. Pegge verfasserin aut Hannie Kremer verfasserin aut Cris P. Lanting verfasserin aut Ronald J. E. Pennings verfasserin aut In Genes MDPI AG, 2010 14(2023), 2, p 457 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:2, p 457 https://doi.org/10.3390/genes14020457 kostenfrei https://doaj.org/article/2dc7721b383843beb3f210caf5cd5229 kostenfrei https://www.mdpi.com/2073-4425/14/2/457 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2, p 457
spelling	10.3390/genes14020457 doi (DE-627)DOAJ080282474 (DE-599)DOAJ2dc7721b383843beb3f210caf5cd5229 DE-627 ger DE-627 rakwb eng QH426-470 Hedwig M. Velde verfasserin aut Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods. hereditary hearing loss <i<WFS1</i< DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss Genetics Xanne J. J. Huizenga verfasserin aut Helger G. Yntema verfasserin aut Lonneke Haer-Wigman verfasserin aut Andy J. Beynon verfasserin aut Jaap Oostrik verfasserin aut Sjoert A. H. Pegge verfasserin aut Hannie Kremer verfasserin aut Cris P. Lanting verfasserin aut Ronald J. E. Pennings verfasserin aut In Genes MDPI AG, 2010 14(2023), 2, p 457 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:2, p 457 https://doi.org/10.3390/genes14020457 kostenfrei https://doaj.org/article/2dc7721b383843beb3f210caf5cd5229 kostenfrei https://www.mdpi.com/2073-4425/14/2/457 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2, p 457
allfields_unstemmed	10.3390/genes14020457 doi (DE-627)DOAJ080282474 (DE-599)DOAJ2dc7721b383843beb3f210caf5cd5229 DE-627 ger DE-627 rakwb eng QH426-470 Hedwig M. Velde verfasserin aut Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods. hereditary hearing loss <i<WFS1</i< DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss Genetics Xanne J. J. Huizenga verfasserin aut Helger G. Yntema verfasserin aut Lonneke Haer-Wigman verfasserin aut Andy J. Beynon verfasserin aut Jaap Oostrik verfasserin aut Sjoert A. H. Pegge verfasserin aut Hannie Kremer verfasserin aut Cris P. Lanting verfasserin aut Ronald J. E. Pennings verfasserin aut In Genes MDPI AG, 2010 14(2023), 2, p 457 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:2, p 457 https://doi.org/10.3390/genes14020457 kostenfrei https://doaj.org/article/2dc7721b383843beb3f210caf5cd5229 kostenfrei https://www.mdpi.com/2073-4425/14/2/457 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2, p 457
allfieldsGer	10.3390/genes14020457 doi (DE-627)DOAJ080282474 (DE-599)DOAJ2dc7721b383843beb3f210caf5cd5229 DE-627 ger DE-627 rakwb eng QH426-470 Hedwig M. Velde verfasserin aut Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods. hereditary hearing loss <i<WFS1</i< DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss Genetics Xanne J. J. Huizenga verfasserin aut Helger G. Yntema verfasserin aut Lonneke Haer-Wigman verfasserin aut Andy J. Beynon verfasserin aut Jaap Oostrik verfasserin aut Sjoert A. H. Pegge verfasserin aut Hannie Kremer verfasserin aut Cris P. Lanting verfasserin aut Ronald J. E. Pennings verfasserin aut In Genes MDPI AG, 2010 14(2023), 2, p 457 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:2, p 457 https://doi.org/10.3390/genes14020457 kostenfrei https://doaj.org/article/2dc7721b383843beb3f210caf5cd5229 kostenfrei https://www.mdpi.com/2073-4425/14/2/457 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2, p 457
allfieldsSound	10.3390/genes14020457 doi (DE-627)DOAJ080282474 (DE-599)DOAJ2dc7721b383843beb3f210caf5cd5229 DE-627 ger DE-627 rakwb eng QH426-470 Hedwig M. Velde verfasserin aut Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods. hereditary hearing loss <i<WFS1</i< DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss Genetics Xanne J. J. Huizenga verfasserin aut Helger G. Yntema verfasserin aut Lonneke Haer-Wigman verfasserin aut Andy J. Beynon verfasserin aut Jaap Oostrik verfasserin aut Sjoert A. H. Pegge verfasserin aut Hannie Kremer verfasserin aut Cris P. Lanting verfasserin aut Ronald J. E. Pennings verfasserin aut In Genes MDPI AG, 2010 14(2023), 2, p 457 (DE-627)614096537 (DE-600)2527218-4 20734425 nnns volume:14 year:2023 number:2, p 457 https://doi.org/10.3390/genes14020457 kostenfrei https://doaj.org/article/2dc7721b383843beb3f210caf5cd5229 kostenfrei https://www.mdpi.com/2073-4425/14/2/457 kostenfrei https://doaj.org/toc/2073-4425 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2023 2, p 457
language	English
source	In Genes 14(2023), 2, p 457 volume:14 year:2023 number:2, p 457
sourceStr	In Genes 14(2023), 2, p 457 volume:14 year:2023 number:2, p 457
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	hereditary hearing loss <i<WFS1</i< DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss Genetics
isfreeaccess_bool	true
container_title	Genes
authorswithroles_txt_mv	Hedwig M. Velde @@aut@@ Xanne J. J. Huizenga @@aut@@ Helger G. Yntema @@aut@@ Lonneke Haer-Wigman @@aut@@ Andy J. Beynon @@aut@@ Jaap Oostrik @@aut@@ Sjoert A. H. Pegge @@aut@@ Hannie Kremer @@aut@@ Cris P. Lanting @@aut@@ Ronald J. E. Pennings @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	614096537
id	DOAJ080282474
language_de	englisch
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callnumber-first	Q - Science
author	Hedwig M. Velde
spellingShingle	Hedwig M. Velde misc QH426-470 misc hereditary hearing loss misc <i<WFS1</i< misc DFNA6/14/38 misc human genetics misc autosomal dominant hearing loss misc low-frequency sensorineural hearing loss misc Genetics Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38
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topic_title	QH426-470 Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38 hereditary hearing loss <i<WFS1</i< DFNA6/14/38 human genetics autosomal dominant hearing loss low-frequency sensorineural hearing loss
topic	misc QH426-470 misc hereditary hearing loss misc <i<WFS1</i< misc DFNA6/14/38 misc human genetics misc autosomal dominant hearing loss misc low-frequency sensorineural hearing loss misc Genetics
topic_unstemmed	misc QH426-470 misc hereditary hearing loss misc <i<WFS1</i< misc DFNA6/14/38 misc human genetics misc autosomal dominant hearing loss misc low-frequency sensorineural hearing loss misc Genetics
topic_browse	misc QH426-470 misc hereditary hearing loss misc <i<WFS1</i< misc DFNA6/14/38 misc human genetics misc autosomal dominant hearing loss misc low-frequency sensorineural hearing loss misc Genetics
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title	Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38
ctrlnum	(DE-627)DOAJ080282474 (DE-599)DOAJ2dc7721b383843beb3f210caf5cd5229
title_full	Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38
author_sort	Hedwig M. Velde
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author_browse	Hedwig M. Velde Xanne J. J. Huizenga Helger G. Yntema Lonneke Haer-Wigman Andy J. Beynon Jaap Oostrik Sjoert A. H. Pegge Hannie Kremer Cris P. Lanting Ronald J. E. Pennings
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class	QH426-470
format_se	Elektronische Aufsätze
author-letter	Hedwig M. Velde
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author2-role	verfasserin
title_sort	genotype and phenotype analyses of a novel <i<wfs1</i< variant (c.2512c<t p.(pro838ser)) associated with dfna6/14/38
callnumber	QH426-470
title_auth	Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38
abstract	The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods.
abstractGer	The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods.
abstract_unstemmed	The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic <i<WFS1</i< variant (NM_006005.3:c.2512C<T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (<i<n</i< = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel <i<WFS1</i< variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified <i<WFS1</i< variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods.
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title_short	Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38
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Genotype and Phenotype Analyses of a Novel <i<WFS1</i< Variant (c.2512C<T p.(Pro838Ser)) Associated with DFNA6/14/38

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