Genotype–Phenotype Relationship in Inherited Disorders of Hearing Impairment

Abstract

Hearing impairment is a genetically heterogeneous disorder. Many causative genes have been described, and the number is still expanding. Nonsyndromic hearing impairment has several clinical characteristics that may point into the direction of a certain gene, but this is not often the case. Syndromic hearing impairment is characterised by additional clinical symptoms, which may direct diagnostics towards the analysis of specific genes. However, the distinction between nonsyndromic hearing impairment and the syndromic forms of the disorder is becoming blurred when looking at the causative genes. The spectrum of mutations from mild to severe in one gene can lead to completely different clinical symptoms, and the phenotype–genotype relation is ever expanding. The molecular diagnosis of hearing impairment is challenging but has benefited tremendously from the introduction of massive parallel sequencing techniques.

Key Concepts

  • Hearing impairment can be syndromic or nonsyndromic, but extensive overlap exists in the genes involved.
  • Specific clinical characteristics of nonsyndromic hearing impairment have limited value in determining which gene is involved.
  • Syndromic hearing impairment is caused by a plethora of genes, and severe versus mild mutations in the same gene can lead to very different phenotypes.
  • Molecular diagnosis of hearing impairment is preferably done using massive parallel sequencing techniques.
  • In the coming years more genes will be discovered to be involved in hearing impairment.

Keywords: characteristics of hearing impairment; audiogram; DFNB; DFNA; DFNX; Usher syndrome; Heimler syndrome; massive parallel sequencing; exome sequencing

Figure 1. Examples of typical audiograms found in sensorineural hearing impairment: only AC thresholds are shown, BC thresholds were consistent without airbone gaps. (a) TMPRSS3 with a ‘ski‐slope’ configuration; (b) TECTA with a ‘cookie‐bite’ configuration and (c) WFS1 with low‐frequency HL.
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Further Reading

Sloan‐Heggen CM, Bierer AO, Shearer AE, et al. (2016) Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. Human Genetics 135: 441–450.

Smith RJH, Shearer AE, Hildebrand MS, et al. (1999) Deafness and Hereditary Hearing Loss Overview [Updated 2014 Jan 9]. In: Pagon RA, Adam MP, Ardinger HH, et al. (eds) GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993‐2017. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1434/.

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How to Cite close
Hoefsloot, Lies H, and Roux, Anne‐Francoise(Jul 2017) Genotype–Phenotype Relationship in Inherited Disorders of Hearing Impairment. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026842]