Common Molecular Etiologies Are Rare in Nonsyndromic Tibetan Chinese Patients with Hearing Impairment

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

Genotypes of GJB2 gene in Tibetan patients with hearing loss and Tibetan controls.

<p>TM, transmembrane domain; EC, extracellular domain; IC, intracellular domain.</p><p>Note: p.V37I is controversy variant, see the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0030720#s4" target="_blank">discussion</a>.</p

Genotypes and phenotype of SLC26A4 gene in Tibetan patients with hearing loss.

<p>nl, normal; EVA, enlarged vestibular aqueduct; IVS7, intravening sequence 7 (intron 7); IVS13, intravening sequence 13 (intron 13);IVS15, intravening sequence 15 (intron 15);IVS18, intravening sequence 18 (intron 18);IAC,internal auditory canal.</p

CT images of inner ear malformation in Tibetan patients with hearing impairment.

<p><b>a</b>. incomplete partition type I <b>b</b>. common cavity deforrmity <b>c</b>. malformation of inner ears including cochlea,vestibular and semicircular canals <b>d</b>. malformation of cochlea and enlargement of internal auditory canals <b>e</b>. narrow internal auditory canal <b>f</b>. malformation of vestibular and semicircular canals <b>g</b>. malformation of semicircular canals <b>h</b>. malformation of cochlea <b>i</b>. ossification of the inner ear.</p

Temporal bone CT Scan Phenotype in Chinese Tibetan patients with hearing loss.

<p>Note:One patient shows common cavity deforrmity in the right ear and incomplete partition type I in the left ear.</p