Abstract
Recent progress in gene identification for non-syndromic deafness demonstrates the efficacy of using a large family approach. To assess if clinical and genetic heterogeneity exists in families with non-syndromic hearing impairment we have identified five large Chinese families suitable for investigating clinical and genetic heterogeneity. Five Chinese families spanning 5-6 generations and comprising 48 to 172 members were identified. The auditory phenotype was investigated with pure tone audiometry and DPOAEs. Age at onset of hearing loss was compared between generations by using life-table analysis and the Wilcoxon test in a family. All statistical analyses were performed using the SAS statistical package. Screening for GJB2 and mitochondrial mutations was performed. Two families showing maternal inheritance were found to have the mitDNA A1555G mutation. Subjects with the A1555G mutation exhibit a normal to profound, progressive deafness. Anticipation of the hearing loss was observed in one of these two families. The other three families are segregating for a late onset form of progressive hearing loss with normal vestibular function. DPOAEs from a group of possible gene carriers with normal audiograms in two families have shown a substantial difference from that of controls. Our data show the existence of clinical and genetic heterogeneity in the five large Chinese deaf families. Marked differences in severity of hearing loss, along with a lack of exposure to aminoglycosides and the presence of anticipation in the mitDNA deafness suggest the presence of a modifier. DPOAEs may be a sensitive test for a subclinical change in carriers. Identification of gene(s) for deafness should allow us to better understand the molecular basis of deafness and to improve patient care.