title: Common molecular etiologies are rare in nonsyndromic Tibetan Chinese patients with hearing impairment.
abstract: BACKGROUND
  Thirty thousand infants are born every year with congenital hearing impairment in mainland China. Racial and regional factors are important in clinical diagnosis of genetic deafness. However, molecular etiology of hearing impairment in the Tibetan Chinese population living in the Tibetan Plateau has not been investigated. To provide appropriate genetic testing and counseling to Tibetan families, we investigated molecular etiology of nonsyndromic deafness in this population.
  
  
  METHODS
  A total of 114 unrelated deaf Tibetan children from the Tibet Autonomous Region were enrolled. Five prominent deafness-related genes, GJB2, SLC26A4, GJB6, POU3F4, and mtDNA 12S rRNA, were analyzed. Inner ear development was evaluated by temporal CT. A total of 106 Tibetan hearing normal individuals were included as genetic controls. For radiological comparison, 120 patients, mainly of Han ethnicity, with sensorineural hearing loss were analyzed by temporal CT.
  
  
  RESULTS
  None of the Tibetan patients carried diallelic GJB2 or SLC26A4 mutations. Two patients with a history of aminoglycoside usage carried homogeneous mtDNA 12S rRNA A1555G mutation. Two controls were homozygous for 12S rRNA A1555G. There were no mutations in GJB6 or POU3F4. A diagnosis of inner ear malformation was made in 20.18% of the Tibetan patients and 21.67% of the Han deaf group. Enlarged vestibular aqueduct, the most common inner ear deformity, was not found in theTibetan patients, but was seen in 18.33% of the Han patients. Common molecular etiologies, GJB2 and SLC26A4 mutations, were rare in the Tibetan Chinese deaf population.
  
  
  CONCLUSIONS
  The mutation spectrum of hearing loss differs significantly between Chinese Tibetan patients and Han patients. The incidence of inner ear malformation in Tibetans is almost as high as that in Han deaf patients, but the types of malformation vary greatly. Hypoxia and special environment in plateau may be one cause of developmental inner ear deformity in this population.
authors.affiliation: Department of Otolaryngology, PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
authors.forename: Shasha
authors.initials: S
authors.lastname: Huang
authors.forename: Lujie
authors.initials: L
authors.lastname: Zuo
authors.forename: Guozheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Yueshuai
authors.initials: Y
authors.lastname: Song
authors.forename: Guojian
authors.initials: G
authors.lastname: Wang
authors.forename: Hongtian
authors.initials: H
authors.lastname: Wang
authors.forename: Deliang
authors.initials: D
authors.lastname: Huang
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D044466:Asian People; D000072259:Connexin 26; D000075302:Connexin 30; D017630:Connexins / Q000235:genetics; D034381:Hearing Loss / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D050809:POU Domain Factors / Q000235:genetics; D012335:RNA, Ribosomal / Q000235:genetics; D000076988:Sulfate Transporters; D018609:Tibet
chemical_list: D000075302:Connexin 30; D017630:Connexins; C000607042:GJB2 protein, human; C491020:GJB6 protein, human; D026901:Membrane Transport Proteins; D050809:POU Domain Factors; C091774:POU3F4 protein, human; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D000072259:Connexin 26