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The ancient Silk Road (also called "Northwest Silk Road") in Northwest China, starting from Xi'an, passes through Gansu, Xinjiang, Central Asia, West Asia, and the land passage connecting the Mediterranean countries. The aim of the present study was to determine the frequency of mitochondrial DNA12SrRNA m.1555A>G mutation in a total of 2417 cases of nonsyndromic deaf-mute patients representative of the general population of Shaanxi, Gansu, Qinghai, Ningxia, and Xinjiang along the Silk Road. Enzyme digestion and direct sequencing were applied to identify sequence variations. The carrier frequency of mitochondrial DNA12S rRNA m.1555A>G mutation was estimated to be 5.21% (126/2417) in the studied population. In detail, the carrier frequency of Uighur and Hui was 1.62% (3/185) and 3.29% (10/304), respectively, compared with 6.09% (113/1856) that of Han. There was a statistically significant difference between Uighur and Han (chi-square test, chi(2) = 6.437, p = 0.011 and p < 0.05), whereas no significant difference in m.1555A>G mutation spectrum or prevalence of mitochondrial DNA12SrRNA was found between Uighur and Hui or Hui and Han. In the 126 m.1555A>G mutation carriers, 52 cases were found to have a clear history of using aminoglycoside antibiotics. Results suggested that the application of aminoglycoside antibiotics in this region is an important reason for higher incidence of m.1555A>G mutation in the deaf-mute population.

Background: Mutations in OTOF gene, encoding otoferlin, cause DFNB9 deafness and non-syndromic auditory neuropathy (AN). The aim of this study is to identify OTOF mutations in Chinese patients with non-syndromic auditory neuropathy., Methods: 73 unrelated Chinese Han patients with AN, including one case of temperature sensitive non-syndromic auditory neuropathy (TS-NSRAN) and 92 ethnicity-matched controls with normal hearing were screened. Forty-five pairs of PCR primers were designed to amplify all of the exons and their flanking regions of the OTOF gene. The PCR products were sequenced and analyzed for mutation identification., Results: Five novel possibly pathogenic variants (c.1740delC, c.2975&#95;2978delAG, c.1194T>A, c.1780G>A, c.4819C > T) were identified in the group of 73 AN patients, in which two novel mutant alleles (c.2975&#95;2978delAG + c.4819C > T) were identified in one Chinese TS-NSRAN case. Besides, 10 non-pathogenic variants of the OTOF gene were found in AN patients and controls., Conclusions: Screening revealed that mutations in the OTOF gene account for AN in 4 of 73(5.5%) sporadic AN patients, which shows a lower genetic load of that gene in contrast to the previous studies based on other populations. Notably, we found two novel mutant alleles related to temperature sensitive non-syndromic auditory neuropathy. This mutation screening study further confirms that the OTOF gene contributes to ANs and to TS-NSRAN.

Conclusion: This genetic epidemiological study demonstrated that 26.65% of the prelingual deafness in Northern Chinese patients can be detected at younger ages by genetic testing of three common hearing loss genes (GJB2, SLC26A4 and mtDNA A1555G), and thus, early intervention measures could be undertaken to help them in language acquisition., Objectives: The GJB2, SLC26A4 and mtDNA A1555G mutations are the prevalent causes of prelingual deafness worldwide. Numerous studies have revealed that the forms and frequencies of the mutations in the three genes are largely dependent on the ethnic or geographic origins. Hence, this study aimed to characterize the mutation profiles of the three genes in prelingual deafness in Northern Chinese patients. SUBECTS AND METHODS: An investigation of 514 patients with prelingual deafness and 117 controls with normal hearing was conducted. Bidirectional sequencing (or enzyme digestion) was applied to identify sequence variations., Results: This study revealed that 26.65% patients had two mutated alleles (homozygote or compound heterozygote) of GJB2 (9.14%) or SLC26A4 (8.95%) and/or an mtDNA A1555G (8.56%) mutation. In detail, 19.26% patients carried GJB2 mutations including 10.12% single mutant carriers. 235delC was the most common type, making up 69.18% of all mutants for GJB2. The mutant carrier rate for SLC26A4 was 15.2%, including 6.23% single mutant carriers. The two most common types (IVS7-2A > G and H723R) accounted for 51.61% and 33.06% mutations, respectively. Forty-five patients had mtDNA A1555G, giving a frequency of 8.75%. In the control group with normal hearing, 2.56%, 1.71% and 0% of the subjects carried a single mutant for GJB2, SLC26A4 and mtDNA A1555G, respectively.

Objective: To investigate the prevalence of the mitochondrial DNA (mtDNA) A1555G mutation in nonsyndromic hearing impairment (NSHI) patients from Gansu province., Methods: Subjects included 802 students selected from five Deaf-Mute Schools in Gansu. DNA was extracted from peripheral blood of all patients. The mitochondrial DNA target fragments were amplified by polymerase chain reaction (PCR). The Mutations were detected by AIw26I digestion and sequence analysis., Results: The homoplasmic A1555G mutation was found in 67 individuals from 802 patients (8.4%). Fifteen of these 67 patients had family histories., Conclusions: The mtDNA A1555G mutation had a higher incidence in Gansu population with nonsyndromic hearing impairment than other studies. The data not only gaven more evidences that the prevalence of mtDNA A1555G mutation in china was higher than that in Europe and America, but also gaven valuable information for gene diagnosis, genetic counseling and would improve the safety of aminoglycoside antibiotic therapy.

Objective: To map the gene locus in a Chinese pedigree with autosomal dominant nonsyndromic hearing loss., Methods: A genome wide screening was performed with 394 microsatellite markers distributed with an average spacing of 10 cM (ABI Prism Linkage Mapping Set 2, Applied Biosystems, Foster City, CA, U.S.A.)., Results: Affected family members showed a bilateral, symmetrical, progressive neurosensory deafness. Significant linkage was found to marker D1 S937 (maximum two point LOD score of 5. 71 at theta = 0.05) on chromosome 11q. The position of the novel deafness locus, DFNA11, was delimited by analysis of the recombinant haplotypes (D11S165-D11S1874). This analysis placed DFNA11 between the proximal marker D11S1314 and the distal marker D11S898, which define a critical interval of 25.34 cM., Conclusions: Mapping of the DFNA11 locus further confirms the great genetic heterogeneity underlying the autosomal dominant forms of hereditary deafness. Reports of more families with hearing impairment linked to this locus should contribute to the identification of the responsible gene, providing insights into the auditory function and the molecular pathophysiology of age related hearing loss.