EMQN Best Practice guidelines for diagnostic testing of mutations causing non-syndromic hearing impairment at the DFNB1 locus

Hoefsloot, Lies H.; Roux, Anne‐Françoise; Bitner‐Glindzicz, Maria

doi:10.1038/ejhg.2013.83

Cited by 32 publications

(35 citation statements)

References 58 publications

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“…In the Caucasian population, the most common mutation has a carrier frequency of 1:45 (suppl 6). The frequency of carriership at least for some populations studied is between 1% and 3% (suppl 6-11), with exceptions for certain other populations (suppl [12][13][14], such as the African-American population (suppl 15). The locus was identified in 1994 (suppl 16), and the GJB2 gene in that locus has been one of the first causative genes to be found (suppl 17,18).…”

Section: Gjb2 and Gjb6: Dfnb1mentioning

confidence: 93%

Genotype phenotype correlations for hearing impairment: Approaches to management

et al. 2014

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Hearing impairment is an extremely heterogeneous disorder, with both environmental as well as genetic causes. This review describes the known genes involved in non-syndromic hearing impairment and their genotype-phenotype correlations where possible. Furthermore, some of the more frequent syndromic forms of hearing impairment are described, in particular where they overlap with the non-syndromic forms. Given the heterogeneity of the disorder, together with the indistinguishable phenotypes for many of the genes, it is suggested that testing for mutations is performed using massive parallel sequencing techniques, either by a large targeted set of genes or by an exome wide analysis.

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Section: Gjb2 and Gjb6: Dfnb1mentioning

confidence: 93%

Genotype phenotype correlations for hearing impairment: Approaches to management

et al. 2014

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“…Both patients (family B and C) selected for WES also fulfilled the criteria used for database searching. In all probands (n = 30) we have performed sequencing of the whole coding region of the GJB2 gene, as well as testing for GJB6 deletions and two most common mitochondrial mutations (m. A1555G, m.A3243G) according to the best practice guidelines for the molecular genetics diagnosis of HL [17]. …”

Section: Methodsmentioning

confidence: 99%

Novel and De Novo Mutations Extend Association of POU3F4 with Distinct Clinical and Radiological Phenotype of Hearing Loss

et al. 2016

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POU3F4 mutations (DFNX2) are the most prevalent among non-syndromic X-linked hearing loss (HL) identified to date. Clinical manifestations of DFNX2 usually comprise congenital HL either sensorineural or mixed, a tendency towards perilymphatic gusher during otologic surgery and temporal bone malformations. The aim of the present study was to screen for POU3F4 mutations in a group of 30 subjects with a suggestive clinical phenotype as well as a group (N = 1671–2018) of unselected hearing loss patients. We also planned to analyze audiological and radiological features in patients with HL caused by POU3F4 defects. The molecular techniques used to detect POU3F4 mutations included whole exome sequencing (WES), Sanger sequencing and real-time polymerase chain reaction. Hearing status was assessed with pure-tone audiometry and auditory brainstem response. Computer tomography scans were evaluated to define the pattern of structural changes in the temporal bones. Six novel (p.Gln27*, p.Glu187*, p.Leu217*, p.Gln275*, p.Gln306*, p.Val324Asp) and two known (p.Ala116fs141*, p.Leu208*) POU3F4 mutations were detected in the studied cohort. All probands with POU3F4 defects suffered from bilateral, prelingual, severe to profound HL. Morphological changes of the temporal bone in these patients presented a similar pattern, including malformations of the internal auditory canal, vestibular aqueduct, modiolus and vestibule. Despite different localization in the POU3F4 gene all mutations severely impair the protein structure affecting at least one functional POU3F4 domain, and results in similar and severe clinical manifestations. Sequencing of the entire POU3F4 gene is recommended in patients with characteristic temporal bone malformations. Results of POU3F4 mutation testing are important not only for a proper genetic counseling, but also for adequate preparation and conduction of a surgical procedure.

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“…Genomic DNA was isolated with a standard salting-out procedure or using an automatic method (Maxwell RSC Instrument, Promega, Walldorf, Germany), respectively. Genetic testing of the DFNB1 locus was performed according to recommendations of the European Molecular Quality Network (EMQN) [14]. In all patients, a tree-step molecular examination procedure was applied.…”

Section: Genetic Testingmentioning

confidence: 99%

Cochlear Implantation Outcome in Children with DFNB1 locus Pathogenic Variants

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Obrycka

Lorens

et al. 2020

JCM

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Almost 60% of children with profound prelingual hearing loss (HL) have a genetic determinant of deafness, most frequently two DFNB1 locus (GJB2/GJB6 genes) recessive pathogenic variants. Only few studies combine HL etiology with cochlear implantation (CI) outcome. Patients with profound prelingual HL who received a cochlear implant before 24 months of age and had completed DFNB1 genetic testing were enrolled in the study (n = 196). LittlEARS questionnaire scores were used to assess auditory development. Our data show that children with DFNB1-related HL (n = 149) had good outcome from the CI (6.85, 22.24, and 28 scores at 0, 5, and 9 months post-CI, respectively). A better auditory development was achieved in patients who receive cochlear implants before 12 months of age. Children without residual hearing presented a higher rate of auditory development than children with responses in hearing aids over a wide frequency range prior to CI, but both groups reached a similar level of auditory development after 9 months post-CI. Our data shed light upon the benefits of CI in the homogenous group of patients with HL due to DFNB1 locus pathogenic variants and clearly demonstrate that very early CI is the most effective treatment method in this group of patients.

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EMQN Best Practice guidelines for diagnostic testing of mutations causing non-syndromic hearing impairment at the DFNB1 locus

Cited by 32 publications

References 58 publications

Genotype phenotype correlations for hearing impairment: Approaches to management

Genotype phenotype correlations for hearing impairment: Approaches to management

Novel and De Novo Mutations Extend Association of POU3F4 with Distinct Clinical and Radiological Phenotype of Hearing Loss

Cochlear Implantation Outcome in Children with DFNB1 locus Pathogenic Variants

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