title: Extremely discrepant mutation spectrum of SLC26A4 between Chinese patients with isolated Mondini deformity and enlarged vestibular aqueduct.
abstract: BACKGROUND
  Mutations in SLC26A4 cause Pendred syndrome (hearing loss with goiter) or DFNB4 (non-syndromic hearing loss with inner ear malformation, such as enlarged vestibular aqueduct or Mondini deformity). The relationship between mutations in SLC26A4 and Mondini deformity without enlarged vestibular aqueduct has not been studied in any Chinese deaf population. The purpose of this study was to assess whether mutations in the SLC26A4 gene cause Mondini deformity without an enlarged vestibular aqueduct (isolated Mondini deformity) in a Chinese population.
  
  
  METHODS
  In total, 144 patients with sensorineural hearing loss were included and subjected to high-resolution temporal bone CT. Among them, 28 patients with isolated Mondini dysplasia (MD group), 50 patients with enlarged vestibular aqueduct with Mondini dysplasia (EVA with MD group), 50 patients with enlarged vestibular aqueduct without Mondini dysplasia (EVA group), and 16 patients with other types of inner ear malformations (IEM group) were identified. The coding exons of SLC26A4 were analyzed in all subjects.
  
  
  RESULTS
  DNA sequence analysis of SLC26A4 was performed in all 144 patients. In the different groups, the detection rate of the SLC26A4 mutation differed. In the isolated MD group, only one single allelic mutation in SLC26A4 was found in one patient (1/28, 3.6%). In the EVA with MD group, biallelic and monoallelic SLC26A4 mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. Also, in the EVA group, biallelic and monoallelic SLC26A4 mutations were identified in 46 patients (46/50, 92.0%) and three patients (3/50, 6.0%), respectively. These percentages were identical to those in the EVA plus MD group. Only two patients carried monoallelic mutations of the SLC26A4 gene in the IEM group (2/16, 12.5%). There were significant differences in the frequency of SLC26A4 mutation among the groups (P<0.001). The detection rate of SLC26A4 mutation in the isolated MD group was significantly lower than in the EVA group (with or without MD; P<0.001), and there was no significant difference in the detection rate of SLC26A4 between the MD group and IEM group (P>0.5).
  
  
  CONCLUSIONS
  Although mutations in the SLC26A4 gene were frequently found in Chinese EVA patients with and without MD, there was no evidence to show a relationship between isolated MD and the SLC26A4 gene in the Chinese population examined. Hearing impairment in patients with isolated MD may be caused by factors other than mutations in the SLC26A4 gene.
authors.affiliation: Department of Otolaryngology, PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Huang
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Guojian
authors.initials: G
authors.lastname: Wang
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Yan
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Meng
authors.forename: Min
authors.initials: M
authors.lastname: Dong
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D006309:Hearing / Q000235:genetics; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007223:Infant; D008297:Male; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D016415:Sequence Alignment; D000076988:Sulfate Transporters; D014723:Vestibular Aqueduct / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000503:physiopathology; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters