טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
Ph.D Thesis
Ph.D StudentEngel-Yeger Batya
SubjectHearing Impairments and Deafness Due to Consanguinity:
Genetic Factors and Their Physiological and
Clinical Expressions
DepartmentDepartment of Medicine
Supervisor Professor Emeritus Hillel Pratt


Abstract

Mutations in the gene encoding gap junction protein Connexin 26 (Cx26) are a major cause of non-syndromic recessive hearing loss. The gap junctions affected are thought to participate in potassium recycling in the cochlea.

The purpose of this study was to locate along the auditory pathway sites affected by the abnormal function of these gap junctions.

Auditory function was assessed by distortion product otoacoustic emission (DOPAEs) and auditory brainstem evoked potentials (ABEPs) in 128 subjects from a village with high rates of hearing impairments caused by Cx26 mutations: non-carriers, carriers, homozygotes or compound heterozygotes for three Cx26 mutations. All subjects underwent blood tests for mutation screening, pure tone audiometry, SRT and discrimination tests.

Variable hearing impairments were found among homozygotes and compound heterozygotes according to audiometry and ABEPs. DPOAEs were absent except for some sporadic responses. All carriers had significantly smaller DPOAEs compared to non-carriers, although both groups had normal audiograms and ABEPs.

The results indicate that auditory function of homozygotes and compound heterozygotes is similarly affected: outer hair cells (OHCs) are uniformly impaired, with variable inner hair cell / nerve impairment. OHCs mal-function was also found among carriers, as indicated by DPOAEs that are sensitive and may indicate hearing impairments in these subjects as well.

These results suggest that the mutations studied affect the same auditory site - OHCs. Furthermore, for clinical purposes, OAEs provide only partial auditory information in populations with high Cx26 mutation rates. Therefore ABEP should also be included in evaluating hearing.