title: Molecular etiology of hearing impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis.
abstract: BACKGROUND
  The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study.
  
  
  METHODS
  One hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays.
  
  
  RESULTS
  Twenty-six patients (19.26%, 26/135) were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed.
  
  
  CONCLUSIONS
  In Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135) of the patients with hearing loss. Together with GJB2 (23/135), SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the temporal bone CT scan to find EVA and inner ear malformation patients. This model has a unique advantage in epidemiologic study of large deaf population.
authors.affiliation: Department of Otolaryngology and Genetic Testing Center for Deafness, Chinese PLA General Hospital, Beijing, PR China. daipu301@vip.sina.com
authors.forename: Pu
authors.initials: P
authors.lastname: Dai
authors.forename: Yongyi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Deliang
authors.initials: D
authors.lastname: Huang
authors.forename: Xiuhui
authors.initials: X
authors.lastname: Zhu
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Dongyang
authors.initials: D
authors.lastname: Kang
authors.forename: Huijun
authors.initials: H
authors.lastname: Yuan
authors.forename: Bailin
authors.initials: B
authors.lastname: Wu
authors.forename: Dongyi
authors.initials: D
authors.lastname: Han
authors.forename: Lee-Jun C
authors.initials: LJ
authors.lastname: Wong
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000595:Amino Acid Sequence; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D000072259:Connexin 26; D017630:Connexins; D004252:DNA Mutational Analysis; D007758:Ear, Inner / Q000002:abnormalities; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D034381:Hearing Loss / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D016415:Sequence Alignment; D000076988:Sulfate Transporters; D013577:Syndrome; D013961:Thyroid Gland / Q000033:anatomy & histology; D013963:Thyroid Hormones / Q000378:metabolism; D055815:Young Adult
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D026901:Membrane Transport Proteins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters; D013963:Thyroid Hormones; D000072259:Connexin 26