A conference on the molecular biology of hearing and deafness was held in La Jolla, California from 1-4 May 1992, under the sponsorship of the Deafness Research Foundation, The National Institute of Deafness, and the University of California at San Diego.
Of the first two sessions, devoted mainly to animal studies, one concerned development, growth and regeneration. The large number of different growth factors that have now been described was emphasised; they appear to overlap in their distributions and functions in the developing embryo. The other, on inner ear mutations in animals, included a review of positional cloning of genes for deafness in mice and the description of new insertional mutations and disruptions. In these mutations there were malformations of the vestibular part of the inner ear and in three of them a flanking clone on one side of the insertion has been described. A mouse model of the X-linked Alport syndrome involved disruption of the collagen 4a5 gene.
But human genetics provided the bulk of the interest. Advance in knowledge of mutations in the Waardenburg syndrome has recently been especially rapid, particularly in the PAX3 gene where six mutations involving deletions of 18 base pairs, 14 base pairs, 2 base pairs and a single base pair have been described, and two dis-sense mutations. In a case of Waardenburg type 3, the PAX3 gene is deleted together with others on chromosome 2q. Localisations of three further genes for human deafness were announced, a gene for BOR syndrome on 8q, two genes for Usher syndrome on 11q and 11p. The heterogeneity of the disease is now firmly established. In one kindred with maternally inherited deafness there appears to be mitochondrial inheritance together with homozygosity for an autosomal recessive. The several genes causing deafness on the X chromosome were reviewed by Professor Pembrey.
There were sessions on neuronal receptors, on molecular and cell biology studies of the auditory system, gene cloning in the normal labyrinth, and ion channels and transport systems. The molecular biology of temporal bone disease and clinical applications of gene related research was the topic of the last afternoon of the conference,. The finding of measles virus sequences in material from active otosclerosis, molecular investigations of hearing loss associated with autoimmunity, and the use of molecular techniques to identify infectious agents in middle or inner ear infection, were described. Looking ahead, the use of gene therapy to treat hearing impairment appeared within the bounds of possibility.