| Auditory neuropathy is a presently well known hearing loss disorder that has special clinical manifestation. It can be found from infants to adults, in which the patient displays auditory characteristics consistent with normal outer hair cell function and abnormal neural function at the level of the VIIIth (vestibule-cochlear) nerve. These characteristics can be observed in clinical audiologic tests as normal otoacoustic emissions (OAEs) in the presence of an absent or severely abnormal auditory brainstem response (ABR). Pure-tone audiometric thresholds are quite variable in auditory neuropathy patients and can range from normal to severe or profound hearing loss. In many but not all patients with auditory neuropathy, speech discrimination score is poorer than that would be predicted from the pure-tone audiometry. The acoustic reflex is abnormal. In other organs and systems of the patient, no pathological changes can be observed in radiological tests.Several factors have been linked to auditory neuropathy. However, no clear cause and effect relationship has been proved. Some patients that have been diagnosed with auditory neuropathy experienced certain health problems including hereditary, immune diseases, infections, toxicosis and metabolism disorders. The genetic research of auditory neuropathy is still in primary stage and few relative genes contributed to the disorder. From 1980 to now, when the first case of auditory neuropathy was reported, most of cases are sporadic. In recent years, it is reported that auditory neuropathy occurred in some families, which suggests that genetic factors may be involved.In our study, candidate approach was performed on the genotype and phenotype interaction in the cases with auditory neuropathy as well as in the low-frequency hearing loss cases and controls. Mutation screening was carried out in the genes of WFS1 and OTOF. The present study was composed of three parts asbelow:PART 1: clinical recruitmentAudiological examination data of a consanguineous kindred of auditory neuropathy named Z015 family, a number of sporadic cases with auditory neuropathy, a pedigree with low frequence hearing loss named F013 family and some other normal controls were described in this part. The general physical examination results as well as the genealogy of pedigrees were included.PART 2: screening the mutation of WFSl gene in auditory neuropathy.The mutations in the WFSl gene are a common cause of low frequence sensorineural hearing loss, which had been linked to loci designated DFNA6 /14/38. The WFSl gene is located on 4pl6. It contains 8 exons, spanning 33.4 kb of genomic DNA coding for a predicted 890-amino acid transmembrane protein. The protein can be expressed in various tissues, including brain and pancreas. At both the protein and mRNA level, WFSl was present predominantly in selected neurons in the central nerve system.In the study, we designed 14 pairs of primers to amplify 8 exons of the WFSl gene. Polymerase chain reaction (PCR) and sequencing were performed to identify the mutations in PCR products of WFSl coding sequence in the members of groups that involved pedigree and isolated patients suffered from auditoryneuropathy and people as control.Nine mutations located on exon 8 were found in all subjects (2264C/A , 2328A/G, 2328A>G, 2603G>A , 2735A>G , 2766G/A, 2890T>C 2933C/T, 2933C>T , 2934C>T, 2992G>A , 2992G/A) . The mutation 2328A>G and 2766A>G were only existed in the patient with auditory neuropathy and their relative family members. The mutations may cause the amino acid changes(720I>V and 866D>N). At the mutation of 2328A>G locus, a restriction endonuclease site was found and the mutation was detected by the restriction endonuclease to further proved the genotype in the cases.PART 3: screening the mutation of OTOF gene in auditory neurophathy.The OTOF gene is responsible for a form of nonsyndromic deafness (DFNB9) located on region of chromosome 2p23.1. It contains 30 exons, spanning 102.3 kb of genomic DNA. The OTOF gene expression was previously...
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