Audiometric, Vestibular, and Genetic Aspects of a DFNA9 Family with a G88E COCH Mutation

Abstract

Apart from a significantly lower frequency of vestibular areflexia between the ages of 40 and 56 years, there are no phenotypic differences between carriers of the G88E and P51S mutations in the COCH gene.

Clinical Characteristics of a Dutch DFNA9 Family with a Novel <i>COCH</i> Mutation, G87W

“…Mean vestibulo-ocular reflex time constant T plotted against age for the G87W mutation carriers (open circles and solid curve). The dotted and dashed curves are identical to similarly fitted curves previously established for G88E and P51S mutation carriers, respectively [Bischoff et al, 2005;Kemperman et al, 2005].…”

“…The asterisks represent single snapshot measurements for those patients with only presbyacusis [De Leenheer et al, 2002] who had matching ages and levels of hearing impairment. and longitudinal individual (binaural mean air-conduction threshold) measurements (small symbols, different ones for each G87W mutation carrier, with connection lines) are shown for the present family without any fitted curve, together with sigmoidal lines that are identical with the curves presented for the G88E mutation carriers (dotted line) and the measurements for the P51S mutation carriers (dashed lines) included in the report by Kemperman et al [2005]. There are two dashed curves for P51S carriers, the uppermost one fitted to the original threshold data, the lowermost fitted to the same data corrected for zero offset threshold at age zero.…”

“…We were therefore unable to reliably fit the steeply sloping part of the sigmoidal curve to the threshold-on-age data for each frequency. This steep part of the sigmoidal curve corresponds to the rapid progression of hearing impairment that has been shown to occur in mid-age P51S and G88E mutation carriers [Bischoff et al, 2005;Kemperman et al, 2005]. In figure 2 the sigmoidal curves fitted to audiometric data of several P51S families [Bischoff et al, 2005] and of a Dutch G88E family are added for comparison to the present G87W family.…”

“…For comparison, the sigmoidal curves previously fitted to the data of G88E and P51S mutation carriers [Bischoff et al, 2005;Kemperman et al, 2005] are included in figure 2 , showing that the development of hearing impairment in the present G87W mutation carriers resembles that in the G88E and P51S mutation carriers. For the G88E mutation carriers a distinct tendency to show later onset ages and/or relatively more limited impairment in the high frequency range at the more advanced ages can be noticed.…”

Expression studies of osteoglycin/mimecan (OGN) in the cochlea and auditory phenotype of Ogn-deficient mice

“…COCH was chosen as a candidate for hearing loss due to its high expression in the Morton fetal cochlear cDNA library (Robertson et al, 1994;Robertson et al, 1997). Mutations in the gene have since been found to be responsible for DFNA9 in a number of families around the world (Robertson et al, 1998;de Kok et al, 1999;Fransen et al, 1999;Kamarinos et al, 2001;Usami et al, 2003;Nagy et al, 2004;Kemperman et al, 2005;Street et al, 2005;Collin et al, 2006;Pauw et al, 2007). But, although this relationship is well-established, mice deficient in Coch do not exhibit hearing loss (Makishima et al, 2005).…”