| Summary: | 碩士 === 國立臺灣大學 === 臨床醫學研究所 === 95 === Background and Objective
Hearing loss is the most common congenital sensory defect: approximately 1/1000 newborns are affected by severe hearing impairment. Congenital hearing loss (CHL) is composed of a plethora of disease entities. Of which, auditory neuropathy (AN) is of specific interest because of its unique clinical manifestations. Recently, AN has been documented to be associated with mutations in OTOF gene. Although the first AN case in Taiwan was reported by NTUH in 1998, largely remains unknown regarding its prevalence and etiology in Taiwanese patients with CHL. According, we conducted the present study to clarify the epidemiologic significance of AN and inspect the genetic characteristics in Taiwanese patients with AN.
Study design and Methods
The present project includes an epidemiologic study and a genetic study. In the epidemiologic study, we retrospectively reviewed the clinical data in 706 CHL children who were diagnosed at NTUH from 2000 to 2006. We investigated the prevalence of AN in the cohort, and analyzed the clinical features associated with AN. In the genetic study, we screened mutations in OTOF gene in 17 AN families and explored the genotype-phenotype correlations.
Results
Among the 706 CHL children at our clinic, 13 (1.8%) revealed positive otoacoustic emissions (OAEs) and abnormal auditory brainstem response (ABR), thus fulfilling the diagnostic criteria of AN. In total, 22 subjects were recruited in this study, including another 9 subjects referred from other hospitals. The associated audiologic features included progressive, prelingual, bilateral moderate to severe sensorineural hearing loss with a flat-type audiogram configuration. Among the probands of the 17 AN families enrolled for genetic study, mutations in OTOF gene were identified in 3 (18%) probands. All the 3 probands were homozygous for a novel mutation, E1700Q (5098G>C). E1700Q was not identified in a panel of 50 normal
controls, co-segregated with the phenotype of deafness in the 3 pedigrees and is evolutionarily highly conserved, conferring its pathogenicity for AN. We are currently genotyping SNPs in the vicinity of E1700Q to elucidate whether the mutation arises from a common ancestor or not.
Conclusion
Auditory neuropathy (AN) is not rare in Taiwanese children with CHL, and a portion of the AN patients can be attributed to mutations in OTOF gene. A novel OTOF mutation, E1700Q, was identified in the present study, implicating a distinct OTOF mutation spectrum in Taiwanese patients with AN.
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