Hereditary deafness: lessons for developmental studies and genetic diagnosis

Hereditary deafness is highly heterogeneous genetically, with over 100 loci so far identified. Routine diagnostic mutation screening can be done only when a candidate gene has been identified, and preferably a candidate mutat ion. For syndromic forms of hearing loss it is often possible to predict th e gene involved. Non-syndromic loss is much more intractable to diagnostic mutation screening because of the extensive locus heterogeneity. However, m utations in the connexin 26 (GJB2) gene and the mitochondrial m.1555A > G m utation are sufficiently frequent in some populations to justify mutation t esting. Identifying the genes mutated in syndromic hearing loss can help de lineate developmental pathways. Conclusion The example of Waardenburg syndrome is used to illustrate how un ravelling developmental pathways can be more complicated than defining meta bolic pathways through biochemical defects. Developmental genes tend to be organised into networks rather than linear pathways, and transcription fact ors act in a combinatorial manner. This makes developmental pathways harder to unravel genetically than metabolic pathways.