Apparent phenotypic anticipation in autosomal dominant connexin 26 deafness
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Meirav Sokolov
Abstract
Background: Connexin 26 (GJB2) mutations are associated with various types of hearing loss, either without associated symptoms or with skin disease, constituting a form of syndromic hearing loss. These mutations can lead to deafness in either a recessive or a dominant autosomal form of inheritance.
Methods: Ascertainment of a Jewish Ashkenazi family with nonsyndromic hearing loss led to the construction of a pedigree for a four-generation family, with hearing loss detected in three successive generations. The entire coding region of the GJB2 gene was amplified and sequenced by Sanger sequencing.
Results: Audiological analysis revealed that the age of onset and severity of hearing loss were earlier and more severe, respectively, in each successive generation of an Ashkenazi Jewish family. A mutation, c.224G>A, leading to missense p.Arg75Gln was detected only in the affected members of the family.
Conclusions: The entire coding region of GJB2 should be checked in hearing-impaired patients by Sanger sequencing, rather than examination only of the two most prevalent mutations, regardless of mode of inheritance or ethnicity. Furthermore, predictions regarding phenotype based on genotype can be difficult to make due to clinical variability in multigenerational families, as demonstrated in the family presented in this study.
Acknowledgments
This work was supported by the National Institutes of Health (NIDCD), R01DC011835, and I-CORE Gene Regulation in Complex Human Disease Center, no. 41/11.
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
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©2014 by De Gruyter
Artikel in diesem Heft
- Frontmatter
- Editorial
- Israel Society for Auditory Research (ISAR): 2014 Annual Scientific Conference
- Mini Review
- Investigation of the mechanism of soft tissue conduction explains several perplexing auditory phenomena
- Original Articles
- The mechanism of direct stimulation of the cochlea by vibrating the round window
- Auditory-evoked cortical activity: contribution of brain noise, phase locking, and spectral power
- Rapid adaptation to time-compressed speech in young and older adults
- Apparent phenotypic anticipation in autosomal dominant connexin 26 deafness
- The effect of gender on a frequency discrimination task in children
- Auditory Behavior in Everyday Life (ABEL) questionnaire in Hebrew and in Arabic and its association with clinical tests in cochlear-implanted children
- Short-term learning effect in different psychoacoustic measures
- How difficult is difficult? Speech perception in noise in the elderly hearing impaired
- Congress Abstracts
- Israel Society for Auditory Research (ISAR) 2014 Annual Scientific Conference
Artikel in diesem Heft
- Frontmatter
- Editorial
- Israel Society for Auditory Research (ISAR): 2014 Annual Scientific Conference
- Mini Review
- Investigation of the mechanism of soft tissue conduction explains several perplexing auditory phenomena
- Original Articles
- The mechanism of direct stimulation of the cochlea by vibrating the round window
- Auditory-evoked cortical activity: contribution of brain noise, phase locking, and spectral power
- Rapid adaptation to time-compressed speech in young and older adults
- Apparent phenotypic anticipation in autosomal dominant connexin 26 deafness
- The effect of gender on a frequency discrimination task in children
- Auditory Behavior in Everyday Life (ABEL) questionnaire in Hebrew and in Arabic and its association with clinical tests in cochlear-implanted children
- Short-term learning effect in different psychoacoustic measures
- How difficult is difficult? Speech perception in noise in the elderly hearing impaired
- Congress Abstracts
- Israel Society for Auditory Research (ISAR) 2014 Annual Scientific Conference
