Skip to main content
Download PDF

Low frequency of SLC26A4 c.919-2A > G variant among patients with nonsyndromic hearing loss in Yunnan of Southwest China

BMC Medical Genomics volume 17, Article number: 55 (2024) Cite this article

Abstract

Background

Gene variants are responsible for more than half of hearing loss, particularly in nonsyndromic hearing loss (NSHL). The most common pathogenic variant in SLC26A4 gene found in East Asian populations is c.919-2A > G followed by c.2168A > G (p.H723R). This study was to evaluate their variant frequencies in patients with NSHL from special education schools in nine different areas of Southwest China’s Yunnan.

Methods

We performed molecular characterization by PCR-products directly Sanger sequencing of the SLC26A4 c.919-2AG and c.2168 A > G variants in 1167 patients with NSHL including 533 Han Chinese and 634 ethnic minorities.

Results

The SLC26A4 c.919-2A > G variant was discovered in 8 patients with a homozygous state (0.69%) and twenty-five heterozygous (2.14%) in 1167 patients with NSHL. The total carrier rate of the c.919-2A > G variant was found in Han Chinese patients with 4.50% and ethnic minority patients with 1.42%. A significant difference existed between the two groups (P < 0.05). The c.919-2A > G allele variant frequency was ranged from 3.93% in Kunming to zero in Lincang and Nvjiang areas of Yunnan. We further detected the SLC26A4 c.2168 A > G variant in this cohort with one homozygotes (0.09%) and seven heterozygotes (0.60%), which was detected in Baoshan, Honghe, Licang and Pu`er areas. Between Han Chinese group (0.94%) and ethnic minority group (0.47%), there was no statistical significance (P > 0.05). Three Han Chinese patients (0.26%) carried compound heterozygosity for c.919-2A > G and c.2168 A > G.

Conclusion

These data suggest that the variants in both SLC26A4 c.919-2A > G and c.2168 A > G were relatively less frequencies in this cohort compared to the average levels in most regions of China, as well as significantly lower than that in Han-Chinese patients. These results broadened Chinese population genetic information resources and provided more detailed information for regional genetic counselling for Yunnan.

Peer Review reports

Background

Hearing loss (HL) is one of the most prevalent disabilities [1]. There is a broad spectrum of genetic and environmental factors involved in hearing loss [2]. Genetic factors are responsible for more than half of cases. The variants of solute carrier family 26 member 4 (SLC26A4) gene (MIM #605,646), also named the PDS gene, described as the second leading cause after the gap junction protein β 2 (GJB2) gene (MIM #121,011), were responsible for autosomal recessive NSHL (DFNB4, MIM #600,791) and syndromic deafness characterized by congenital sensorineural hearing loss, abnormalities of the cochlea, and goiter named as Pendred syndrome (PS, MIM #274,600) [3, 4].

The SLC26A4 gene, located on chromosome 7q22.q31, contains 21 exons, spans approximately 2343 bp of cDNA and encodes pendrin. Previous research demonstrated that there are hundreds of known variants in the SLC26A4 gene spreading over all exons and their flanking sequences associated with an increased risk of hearing loss [5,6,7]. It was reported that the different ethnic groups and geographical origins have their own distinctive variant hotspot of the SLC26A4 gene with its frequency [8, 9]. In a multiethnic cohort consisting of 117 deaf patients from Turkey (n = 45), Mexico (n = 11) and Iran (n = 61), the most common pathogenic variants of the SLC26A4 gene were c.1197delT (p. C400Vfs*32) and c.1226G > A (p. R409H) [10]. Adhikary et al. observed that SLC26A4 gene variants containing c.1087A > G, c.1195 T > C, c.1363A > T, and c.2145G > T in Indian were found in 215 patients with NSHL [11]. In a meta-analysis, the SLC26A4 c.919-2A > G (rs111033313) in intron 7, c.2168A > G (rs121908362) in exon 19 were the two most common variants in the East Asian population [12]. Particularly, the SLC26A4 c.919-2A > G variant was the most prevalent in China [12, 13], c.2168A > G was predominant in Japan and Korea [14, 15]. However, published work has not been well documented the variant frequencies of c.919-2A > G and c.2168A > G in patients with NSHL in most areas of Southwest China’s Yunnan.

Yunnan, with a unique natural and geographical environment, is located in China's southwest frontier and lives together 52 ethnic populations [16]. Compared to the eastern regions of China, the information on the frequencies of SLC26A4 c.919-2A > G and c.2168A > G variants are still not well known in most areas of Yunnan. In this study, we report the variant frequencies of SLC26A4 c.919-2A > G and c.2168A > G in 1167 patients with NSHL from special education schools in nine different areas of Yunnan, and compared the difference of their frequencies between Han Chinese group and ethnic minority group, among neighboring populations and countries of China. This research enriches the frequency spectrum of the c.919-2A > G and c.2168A > G variants in the Chinese population and contributes to regional genetic counselling and accurate personalized genetic testing.

Methods

Subjects

A total of 1167 unrelated NSHL patients (604 males, 563 females) from special education schools in nine areas of Yunnan were recruited into our study from January 2011 to October 2013. The subjects with NSHL showed bilateral, mild, and severe to profound, sensorineural hearing loss. This cohort consisted of 634 ethnic minorities (54.33%) and 533 ethnic Han Chinese (45.67%). The median age of the patients with NSHL was 13 years (range, 3–27 years). The basic demographics and the distribution of patients with NSHL in nine geographic areas are provided in Table 1 and Fig. 1 according to the China Sixth Census in 2010. The geographical areas from where individuals were recruited are shown in Fig. 1.

Table 1 The demography and the patients with NSHL in nine areas of Yunnan
Full size table
Fig. 1
figure 1

The demographics in nine areas of Yunnan including the counts of participants and SLC26A4 c.919-2A > G and c.2168A > G variants

Full size image

This study received approval from the Ethics Committee of the First People’s Hospital of Yunnan Province and was performed according to the Declaration of Helsinki of 1975, which was revised in 2008. Written informed consent was obtained from all subjects or their parents/guardians. The patients enrolled in this study were diagnosed with NSHL with a medical certificate and our team-based clinical interview, which excluded syndromic hearing loss and consanguinity, brain injury and meningitis. In this cohort, 94 patients (8.05%) had a family history of deafness.

PCR amplification and sanger sequencing

All participants donated their 2 ml peripheral venous blood samples and were collected in EDTAK2-containing tubes. Genomic DNA extraction was performed using a Bioteke Blood DNA Extraction Reagent Kit (BioTeke Corporation, Wuxi, China) according to the manufacturer’s instructions. DNA samples were used to detect variants in SLC26A4 c.919–2 A > G and c.2168A > G by polymerase chain reaction (PCR) amplification followed by Sanger sequencing (ABI 373XL automated DNA sequencer), and analyzed by Genetool software.

Statistical analysis

Data were analyzed using SPSS statistical software (IBM SPSS Statistics for Windows, Version 19.0.). The significance of differences between groups was assessed by the chi-square test. Fisher’s exact test was used to establish the distributions of genotype and allele. A value of P < 0.05 was considered statistically significant. Analysis of data Sequences were compared to the published reference sequence of SLC26A4 (NG_008489, NM_000441).

Results

To identify c.919-2A > G and c.2168A > G variants in the SLC26A4 gene, genomic DNA was extracted, and their regions were amplified by PCR. Amplicons were Sanger sequenced to find c.919-2A > G and c.2168A > G variants.

The distributions of allele and genotypic frequencies of c.919–2 A > G and c.2168A > G in the collected samples were shown in Table 2. Here, we present 1167 patients with NSHL who carried a frequency (2.83%, 33/1167) of SLC26A4 c.919-2A > G variant, with 8 homozygotes (0.69%) and 25 heterozygotes (2.14%), leading to 1.76% allelic frequency. The graphs of DNA sequencing results for c.919–2 A > G and c.2168A > G were shown in Figure S1.

Table 2 The frequencies of SLC26A4 c.919-2A > G and c.2168 A > G variants between the Han Chinese group and the ethnic minority group in NSHL
Full size table

Ethnically, as shown in Table 2, the SLC26A4 c.919–2 A > G variant was found in 4.50% (24/533) of Han Chinese patients and 1.42% (9/634) of minority ethnic patients. Of them, the variant frequencies of heterozygotes and the G allele were 3.56% (19/533) and 2.72% (29/1066) in Han Chinese patients, while there were 0.95% (6/634) and 0.95% (12/1268) in minority ethnic patients, respectively. These differences between the two groups were statistically significant (all P < 0.05). Homozygotes was detected at a lower rate (0.69%, 8/1167), the frequency of homozygotes (0.94%, 5/533) in the Han Chinese group without statistically significant compared to that (0.47%, 3/634) in the minority ethnic group (P = 0.547).

Geographically, a considerable diversity of the SLC26A4 c.919–2 A > G variant frequency in patients with NSHL was shown in Table 3. In nine areas of Yunnan, the allele frequency of the c.919-2A > G variant was the highest in Kunming with 3.93%, compared with that in other areas. The c.919-2A > G variant was not detected in patients from Lincang and Nvjiang areas.

Table 3 The distribution of affected alleles of SLC26A4 c.919-2A > G was found in patients with NSHL in nine different areas of Yunnan
Full size table

We also detected SLC26A4 c.2168 A > G variant in this cohort. A summary of its variant frequency was shown in Table 2. Eight patients (0.69%, 8/1167) were found to harbor c.2168 A > G variant involving five Chinese patients (0.43%) and three ethnic minority patients (0.26%), which were one homozygous and seven heterogeneous. Of them, one ethnic minority patient (0.09%) with homozygous was from Pu`er area, and 2 ethnic minority patients with heterogeneous (0.17%) from Honghe area. Five Han Chinese patients with heterogeneous were from Honghe (0.17%, 2/1167), Baoshan (0.17%, 2/1167) and Lincang (0.09%, 1/1167) areas, respectively.

In this cohort, only three Han Chinese patients (0.26%) carried compound heterozygosity for c.919-2A > G and c.2168 A > G, which 2 patients were from Baoshan and one patient in Honghe areas. Above all, SLC26A4 c.919-2A > G and c.2168 A > G variants were detected at a lower rate among 1167 patients with NSHL in Yunnan compared to the average levels (8.01%, 1.51%) in most of areas of China [17].

The comparisons of the two major pathogenic variant frequencies of SLC26A4 c.919-2A > G and c.2168A > G among neighboring populations and countries of China, and between the Han Chinese group as well as ethnic minority group in China were shown in Tables 4, and 5, respectively. Generally, the distribution trend of c.919-2A > G variant frequency was higher in Eastern and Central regions than the Western regions, the Han Chinese patients harboring more variant frequency than the Ethnic minority patients with NSHL in China.

Table 4 Comparison of the variant frequencies of c.919-2A > G and c.2168 A > G in SLC26A4 gene in patients from neighboring populations and countries of China
Full size table
Table 5 Comparison of the variant frequencies of SLC26A4 c.919-2A > G and c.2168 A > G among Han Chinese and Ethnic minority patients with NSHL in China
Full size table

Discussion

Hearing loss can be caused by a heterogeneous etiology involving genetic and environmental factors [2, 6]. Previous studies supported the SLC26A4 gene, especially the c.919-2A > G followed by c.2168A > G variant, play a critical role in molecular etiology of NSHL in the East Asia population [7,8,9].

In this study, PCR products direct Sanger sequencing was employed to analyze the SLC26A4 c.919-2A > G and c.2168A > G variants in 1167 patients with NSHL from special education schools in nine different areas of Southwest China’s Yunnan, which included 533 Han Chinese and 634 ethnic minorities. The present study shown that 33 (2.83%) out of 1167 NSHL patients carrying SLC26A4 c.919-2A > G variant were detected, and eight patients (0.69%) were found to harbor c.2168 A > G variant. Their allele frequencies were significantly lower (1.76%, 0.40%) than the average levels (8.01%, 1.51%) in most regions of China reported by Yuan and his colleagues [17].

The c.919-2A > G variant frequency in this current study was different from those reported by Dai and other researcher [13, 17, 24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. Dai and colleague demonstrated that 158 homozygotes (4.83%) and 250 heterozygotes (7.64%) of the SLC26A4 c.919-2A > G variants were found in 3271 patients with NSHL from 27 regions of China [13]. Its allele frequency varies widely from 19.94% in Henan to 0.40% in Lhasa of Tibet Autonomous, which was 8.18% in Kunming. Xin’s research demonstrated the c.919-2A > G variant frequency was 4.26% in patients from Kunming [35]. Our results shown that the allele frequency of c.919-2A > G variant was found 3.93% in patients from Kunming. The difference of c.919 A > G variant frequency in the patients from the same area was presented. The reason may be partly explained by sample bias.

Previous studies have revealed that homozygous (biallelic variation) or compound heterozygosity for c.919-2A > G and c.2168 A > G in the SLC26A4 gene was the molecular genetic etiology of sensorineural hearing impairment [9, 11, 12, 15]. In the current study, 8 cases (0.69%) were found to harbor homozygotes of c.919-2A > G, one case (0.09%) with c.2168 A > G homozygotes, and three patients harbored compound heterozygosity for c.919-2A > G and c.2168 A > G. Their variant frequencies were significantly lower compared with the average levels in most regions of China reported by Yuan and Dai et al. [13, 17]. The reasons may be interpreted as follows. First, the c.919-2A > G and c.2168 A > G variants in this cohort may not be the main susceptibility sites to NSHL. Second, there may be small sample bias in this cohort. Third, it can be interpreted in a broader spatial and historical context of population genetics. Yunnan is home not only to Han Chinese but also to 24 officially recognized ethnic minority groups. Populations from different regions of Eurasia as well as Eastern China arrived in Yunnan, and admixed into aborigines with a long history [16]. The present ethnic minority and Han are living together in many places in Yunnan including nine areas in this study, which could have been influenced inter-population marriage. Thus, the homozygote frequency of the SLC26A4 c.919-2A > G variation can be expected to transiently decline according to the Wahlund principles. Therefore, further studies including a larger number of minority ethnic populations and a broad range of geographic areas are needed in the future.

The c.919 A > G variant was the most prevalent in China, while c.2168A > G variant in Japan and Korea [15, 21]. Zhou et al. demonstrated that 57 patients and 20 patients harbored c.919‐2A > G (4.75%) and c.2168A > G (1.67%) variants were found in 1201 patients with NSHL from Shanxi of China [40]. Chen et al. reported five c.919‐2A > G (0.94%) and three c.2168A > G heterozygous (0.57%) were detected in 530 NSHI patients of south China, including Guangdong, Guangxi, Hainan, Hunan, Fujian and Jiangxi Province [41]. Park HJ et al. demonstrated that one SLC26A4 c.919-2A > G homozygote (1.09%) and two c.919-2A > G heterozygotes (2.17%) were detected in 92 deaf Korean probands [21]. The frequency of the SLC26A4 c.919-2A > G allele variant was 0.38% in 264 Japanese individuals [15]. Previous reported that the allele frequency of c.2168A > G variant in patients with NSHL was detected in 2.72%, 4.17%, and 1.51% of Korean, Japanese, and Chinese (mainland Chinese) subjects, respectively [15, 17, 21]. In this study, SLC26A4 c.919-2A > G and c.2168A > G allele variant in patients from Yunnan were rarely lower frequency (0.40%) than that in patients from neighboring populations and countries of China, except from Tibetan Chinese patients with zero. Thus, these results support the variant frequencies of c.919-2A > G and c.2168A > G in SLC26A4 gene dependent on the geographical origin [4, 13, 15, 23, 31,32,33].

Ethnically, the Chinese population consists of 56 ethnic groups. Han Chinese is the largest group. The ethnic minority groups are mainly living in Northwestern and Southwestern of China. Duan et al. reported that the allele frequency of c.919-2A > G was 6.09% (28/460) in Han Chinese patients and 3.33% (14/420) in ethnic minority patients with NSHL from Qinghai in Northwest China [27]. Qing et al. shown that the frequency of the SLC26A4 variant was 7.04% (82/1164), 7.54% (67/888), 5.43% (15/276) among total subjects, the Chinese Han and ethnic minorities patients in Changsha of Hunan [42], respectively. In this study, ethnic minority patients have a lower carrier frequency (0.95%) than that in Han Chinese (2.72%) with statistical significance. The result was in consistence with the previous research shown in Table 5. Above all, these results support the influence of regional or environmental or ethnic origin on the variant frequency of c.919-2A > G and c.2168 A > G in SLC26A4 gene [4, 9, 13, 23, 36].

There are some limitations in this study. Even though this project collected 1167 samples from the wide geographic area of Southwest China’s Yunnan, subjects receiving an imaging examination to identify inner ear status or an enlarged vestibular aqueduct (EVA) and temporal bone abnormalities were unclear. Secondly, Sanger sequencing is the gold-standard for all nucleic acid detection. But compared to the next- generation sequencing (NSG) technology, it cannot find more molecular genetic etiology of deafness. Thirdly, there are absence of information on the hearing levels and some other specific clinical features. Thus, possible genotype–phenotype correlations will be to analysis in the future research.

In conclusion, this study demonstrated that the SLC26A4 c.919-2A > G and c.2168A > G variant frequencies accounted for only a small proportion (1.03%) of patients with NSHL in this cohort. That is, the most common molecular genetic etiology of these patients with NSHL in this cohort is still uncertain. It is probable that hearing loss in these patients is due to variations in other spots in the SLC26A4 gene or other deafness-related genes. Furthermore, these data would facilitate implementation of the frequency spectrum of the SLC26A4 c.919-2A > G variant in the NSHL of the Yunnan population. And, it implied that the SLC26A4 c.919–2 and c.2168A > G are not appropriate for the first step in genetic testing of patients with NSHL in Yunnan.

Availability of data and materials

The data and materials relating to the findings of this study are available from the corresponding author.

References

  1. GBD 2019 Hearing Loss Collaborators. Hearing loss prevalence and years lived with disability, 1990–2019: findings from the Global Burden of Disease Study 2019. Lancet. 2021;397(10278):996–1009.

    Article  Google Scholar 

  2. Meena R, Ayub M. Genetics Of Human Hereditary Hearing Impairment. J Ayub Med Coll Abbottabad. 2017;29(4):671–6.

    PubMed  Google Scholar 

  3. Wasano K, Takahashi S, Rosenberg SK, Kojima T, Mutai H, Matsunaga T, Ogawa K, Homma K. Systematic quantification of the anion transport function of pendrin (SLC26A4) and its disease-associated variants. Hum Mutat. 2020;41(1):316–31.

    Article  CAS  PubMed  Google Scholar 

  4. Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M, Adawi F, Hazani E, Nassir E, Baxevanis AD, Sheffield VC, Green ED. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet. 1997;17(4):411–22.

    Article  CAS  PubMed  Google Scholar 

  5. Lu YJ, Yao J, Wei QJ, Xing GQ, Cao X. Diagnostic Value of SLC26A4 Mutation Status in Hereditary Hearing Loss With EVA: A PRISMA-Compliant Meta-Analysis. Medicine (Baltimore). 2015;94(50):e2248.

    Article  CAS  PubMed  Google Scholar 

  6. Korver AM, Smith RJ, Van Camp G, Schleiss MR, Bitner-Glindzicz MA, Lustig LR, Usami SI, Boudewyns AN. Congenital hearing loss. Nat Rev Dis Primers. 2017;3:16094.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Li XC, Everett LA, Lalwani AK, Desmukh D, Friedman TB, Green ED, Wilcox ER. A mutation in PDS causes non-syndromic recessive deafness. Nat Genet. 1998;18(3):215–7.

    Article  CAS  PubMed  Google Scholar 

  8. Cengiz FB, Yilmazer R, Olgun L, Sennaroglu L, Kirazli T, Alper H, Olgun Y, Incesulu A, Atik T, Huesca-Hernandez F, Domínguez-Aburto J, González-Rosado G, Hernandez-Zamora E, Arenas-Sordo ML, Menendez I, Orhan KS, Avci H, Mahdieh N, Bonyadi M, Foster J 2nd, Duman D, Ozkinay F, Blanton SH, Bademci G, Tekin M. Novel pathogenic variants underlie SLC26A4-related hearing loss in a multiethnic cohort. Int J Pediatr Otorhinolaryngol. 2017;101:167–71.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Tsukada K, Nishio SY, Hattori M, Usami S. Ethnic-specific spectrum of GJB2 and SLC26A4 mutations: their origin and a literature review. Ann Otol Rhinol Laryngol. 2015;124(Suppl 1):61S-76S.

    Article  PubMed  Google Scholar 

  10. Usami S, Nishio SY, Nagano M, Abe S, Yamaguchi T. Deafness Gene Study Consortium. Simultaneous screening of multiple mutations by invader assay improves molecular diagnosis of hereditary hearing loss: a multicenter study. PLoS One. 2012;7(2):e31276.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  11. Adhikary B, Ghosh S, Paul S, Bankura B, Pattanayak AK, Biswas S, Maity B, Das M. Spectrum and frequency of GJB2, GJB6 and SLC26A4 gene mutations among nonsyndromic hearing loss patients in eastern part of India. Gene. 2015;573(2):239–45.

    Article  CAS  PubMed  Google Scholar 

  12. Du W, Guo Y, Wang C, Wang Y, Liu X. A systematic review and meta-analysis of common mutations of SLC26A4 gene in Asian populations. Int J Pediatr Otorhinolaryngol. 2013;77(10):1670–6.

    Article  PubMed  Google Scholar 

  13. Dai P, Li Q, Huang D, Yuan Y, Kang D, Miller DT, Shao H, Zhu Q, He J, Yu F, Liu X, Han B, Yuan H, Platt OS, Han D, Wu BL. SLC26A4 c.919–2A>G varies among Chinese ethnic groups as a cause of hearing loss. Genet Med. 2008;10(8):586–92.

    Article  CAS  PubMed  Google Scholar 

  14. Lee KY, Choi SY, Bae JW, Kim S, Chung KW, Drayna D, Kim UK, Lee SH. Molecular analysis of the GJB2, GJB6 and SLC26A4 genes in Korean deafness patients. Int J Pediatr Otorhinolaryngol. 2008;72(9):1301–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Park HJ, Shaukat S, Liu XZ, Hahn SH, Naz S, Ghosh M, Kim HN, Moon SK, Abe S, Tukamoto K, Riazuddin S, Kabra M, Erdenetungalag R, Radnaabazar J, Khan S, Pandya A, Usami SI, Nance WE, Wilcox ER, Riazuddin S, Griffith AJ. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness. J Med Genet. 2003;40(4):242–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Li Y, Su J, Zhang J, Pei J, Li D, Zhang Y, Li J, Chen M, Zhu B. Targeted next-generation sequencing of deaf patients from Southwestern China. Mol Genet Genomic Med. 2021;9(4):e1660.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yuan Y, Guo W, Tang J, Zhang G, Wang G, Han M, Zhang X, Yang S, He DZ, Dai P. Molecular epidemiology and functional assessment of novel allelic variants of SLC26A4 in non-syndromic hearing loss patients with enlarged vestibular aqueduct in China. PLoS ONE. 2012;7(11):e49984.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tekin M, Akçayöz D, Comak E, Boğoçlu G, Duman T, Fitoz S, Ilhan I, Akar N. Screening the SLC26A4 gene in probands with deafness and goiter (Pendred syndrome) ascertained from a large group of students of the schools for the deaf in Turkey. Clin Genet. 2003;64(4):371–4.

    Article  CAS  PubMed  Google Scholar 

  19. Anwar S, Riazuddin S, Ahmed ZM, Tasneem S, Ateeq-ul-Jaleel, Khan SY, Griffith AJ, Friedman TB, Riazuddin S. SLC26A4 mutation spectrum associated with DFNB4 deafness and Pendred’s syndrome in Pakistanis. J Hum Genet. 2009;54(5):266–70.

    Article  CAS  PubMed  Google Scholar 

  20. Kahrizi K, Mohseni M, Nishimura C, Bazazzadegan N, Fischer SM, Dehghani A, Sayfati M, Taghdiri M, Jamali P, Smith RJ, Azizi F, Najmabadi H. Identification of SLC26A4 gene mutations in Iranian families with hereditary hearing impairment. Eur J Pediatr. 2009;168(6):651–3.

    Article  CAS  PubMed  Google Scholar 

  21. Usami S, Abe S, Weston MD, Shinkawa H, Van Camp G, Kimberling WJ. Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations. Hum Genet. 1999;104(2):188–92.

    Article  CAS  PubMed  Google Scholar 

  22. Erdenechuluun J, Lin YH, Ganbat K, Bataakhuu D, Makhbal Z, Tsai CY, Lin YH, Chan YH, Hsu CJ, Hsu WC, Chen PL, Wu CC. Unique spectra of deafness-associated mutations in Mongolians provide insights into the genetic relationships among Eurasian populations. PLoS ONE. 2018;13(12):e0209797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Danilchenko VY, Zytsar MV, Maslova EA, Bady-Khoo MS, Barashkov NA, Morozov IV, Bondar AA, Posukh OL. Different Rates of the SLC26A4-Related Hearing Loss in Two Indigenous Peoples of Southern Siberia (Russia). Diagnostics (Basel). 2021;11(12):2378.

    Article  CAS  PubMed  Google Scholar 

  24. Wang Y, Chen W, Liu Z, Xing W, Zhang H. Comparison of the Mutation Spectrum of Common Deafness-Causing Genes in 509 Patients With Nonsyndromic Hearing Loss in 4 Different Areas of China by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. J Int Adv Otol. 2021;17(6):492–9.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Liu Y, Ao L, Ding H, Zhang D. Genetic frequencies related to severe or profound sensorineural hearing loss in Inner Mongolia Autonomous Region. Genet Mol Biol. 2016;39(4):567–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Yuan Y, Zhang X, Huang S, Zuo L, Zhang G, Song Y, Wang G, Wang H, Huang D, Han D, Dai P. Common molecular etiologies are rare in nonsyndromic Tibetan Chinese patients with hearing impairment. PLoS ONE. 2012;7(2):e30720.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  27. Duan S, Guo Y, Chen X, Li Y. Genetic mutations in patients with nonsyndromic hearing impairment of minority and Han Chinese ethnicities in Qinghai, China. J Int Med Res. 2021;49(4):3000605211000892.

    Article  CAS  PubMed  Google Scholar 

  28. Pan J, Xu P, Tang W, Cui Z, Feng M, Wang C. Mutation analysis of common GJB2, SCL26A4 and 12S rRNA genes among 380 deafness patients in northern China. Int J Pediatr Otorhinolaryngol. 2017;98:39–42.

    Article  PubMed  Google Scholar 

  29. Zhu J, Cao Q, Zhang N, Ge J, Sun D, Feng Q. A study of deafness-related genetic mutations as a basis for strategies to prevent hereditary hearing loss in Hebei. China Intractable Rare Dis Res. 2015;4(3):131–8.

    Article  PubMed  Google Scholar 

  30. Xie L, Qiu Y, Jin Y, Xu K, Bai X, Liu XZ, Wang XH, Chen S, Sun Y. Hearing Screening Combined with Target Gene Panel Testing Increased Etiological Diagnostic Yield in Deaf Children. Neural Plast. 2021;2021:6151973.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Xiang YB, Tang SH, Li HZ, Xu CY, Chen C, Xu YZ, Ding LR, Xu XQ. Mutation analysis of common deafness-causing genes among 506 patients with nonsyndromic hearing loss from Wenzhou city. China Int J Pediatr Otorhinolaryngol. 2019;122:185–90.

    Article  PubMed  Google Scholar 

  32. Lin Y, Yu F, Jiao Y, Zhou F. Variations in the Mutational Spectrum in Nonsyndromic Hearing Impairment: A study of the Special Schools for the Deaf in Southern China. J Int Adv Otol. 2019;15(2):247–52.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Huang B, Han M, Wang G, Huang S, Zeng J, Yuan Y, Dai P. Genetic mutations in non-syndromic deafness patients in Hainan Province have a different mutational spectrum compared to patients from Mainland China. Int J Pediatr Otorhinolaryngol. 2018;108:49–54.

    Article  PubMed  Google Scholar 

  34. Wu CC, Tsai CY, Lin YH, Chen PY, Lin PH, Cheng YF, Wu CM, Lin YH, Lee CY, Erdenechuluun J, Liu TC, Chen PL, Hsu CJ. Genetic Epidemiology and Clinical Features of Hereditary Hearing Impairment in the Taiwanese Population. Genes (Basel). 2019;10(10):772.

    Article  CAS  PubMed  Google Scholar 

  35. Jiang H, Liu Q, Chen L. Screening and analysis of mutation hot-spots in deafness-associated genes among adolescents with hearing loss. Mol Med Rep. 2015;12(6):8179–84.

    Article  CAS  PubMed  Google Scholar 

  36. Xin F, Yuan Y, Deng X, Han M, Wang G, Zhao J, Gao X, Liu J, Yu F, Han D, Dai P. Genetic mutations in nonsyndromic deafness patients of Chinese minority and Han ethnicities in Yunnan. China J Transl Med. 2013;11:312.

    Article  PubMed  Google Scholar 

  37. Duan SH, Zhu YM, Wang YL, Guo YF. Common molecular etiology of nonsyndromic hearing loss in 484 patients of 3 ethnicities in northwest China. Acta Otolaryngol. 2015;135(6):586–91.

    Article  PubMed  Google Scholar 

  38. Du W, Wang Q, Zhu Y, Wang Y, Guo Y. Associations between GJB2, mitochondrial 12S rRNA, SLC26A4 mutations, and hearing loss among three ethnicities. Biomed Res Int. 2014;2014:746838.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Chen Y, Tudi M, Sun J, He C, Lu HL, Shang Q, Jiang D, Kuyaxi P, Hu B, Zhang H. Genetic mutations in non-syndromic deafness patients of Uyghur and Han Chinese ethnicities in Xinjiang, China: a comparative study. J Transl Med. 2011;9:154.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Zhou Y, Li C, Li M, Zhao Z, Tian S, Xia H, Liu P, Han Y, Ren R, Chen J, Jia C, Guo W. Mutation analysis of common deafness genes among 1,201 patients with non-syndromic hearing loss in Shanxi Province. Mol Genet Genomic Med. 2019;7(3):e537.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Chen K, Zong L, Liu M, Wang X, Zhou W, Zhan Y, Cao H, Dong C, Tang H, Jiang H. Developing regional genetic counseling for southern Chinese with nonsyndromic hearing impairment: a unique mutational spectrum. J Transl Med. 2014;12:64.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Qing J, Zhou Y, Lai R, Hu P, Ding Y, Wu W, Xiao Z, Ho PT, Liu Y, Liu J, Du L, Yan D, Goldstein BJ, Liu X, Xie D. Prevalence of mutations in GJB2, SLC26A4, and mtDNA in children with severe or profound sensorineural hearing loss in southwestern China. Genet Test Mol Biomarkers. 2015;19(1):52–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank the students and their families as well as school teachers for their participation in this study. We are also grateful to teachers from special education schools. The authors would also like to thank the Baoshan School Care for the Deaf and Dumb (Baoshan Area), Dehong Special Education School (Dehong Tai and Jingpo Autonomous Prefecture), Dali Special Education School (Dali Bai Autonomous Prefecture), Honghe Special Education School (Honghe Yir and Hani Autonomous Prefecture), Lijiang Special Education School (Lijiang area), Kunming Huaxia Secondary School (Yunnan Province), Lincang Special Education School (Licang area), Nvjiang School for the Deaf and Dumb (Nvjiang Lisu Autonomous Prefecture), Pu`er Special Education School (Pu`er area), and Tengchong Special Education School (Tengchong city) for their fundamental support and contributions to this work.

Funding

This study was supported by grant from the Project of the National Natural Science Foundation of China (Grant No. 31060155).

Author information

Author notes

  1. Yan-Qiong Li and Heng Ma contributed equality to this work.

Authors and Affiliations

  1. Center for Clinical Medicine Research (Yunnan Provincial Key Laboratory of Clinical Virology, 202205AG070053, L-2019003), The First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology/School of Medicine), Kunming, 650032, Yunnan, China

    Yan-Qiong Li, Qin-Yao Wang, De-Sheng Liu, Wei Wang, Shi-Xin Li, Rong-Xia Zuo, Tao Shen & Ya-Lian Sa

  2. The Outpatient Department of Yanan Hospital Affiliated to Kunming Medical University, Kunming, 650051, Yunnan, China

    Heng Ma

  3. Central Sterile Supply Department, The First People’s Hospital of Yunnan Province, (The Affiliated Hospital of Kunming University of Science and Technology/School of Medicine), Kunming, 650032, Yunnan, China

    Yan-Qiong Li

  4. The Emergency Department of Traditional Chinese Medicine Hospital of Sichuan Province, (The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine), Chengdu, 610075, Sichuan, China

    De-Sheng Liu

  5. Center of Genetic Diagnosis (Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases), The First People’s Hospital of Yunnan Province (The Affiliated Hospital of Kunming University of Science and Technology/School of Medicine), Kunming, 650032, Yunnan, China

    Bao-Sheng Zhu

Authors
  1. Yan-Qiong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heng Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qin-Yao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. De-Sheng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shi-Xin Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rong-Xia Zuo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tao Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bao-Sheng Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Ya-Lian Sa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Li YQ and Ma H collected samples, performed the experiments and prepared the manuscrip. Wang QY conducted the data analysis, drawed and submitted the manuscript. Liu DSH performed the experiments and conducted the data analysis. Wang W and Li SHX participated in the collection the information of patients. Zuo RX participated in the sequence alignment. Shen T and Zhu BS carried out epidemiological survey, and helped to analysis data. Sa YL conceived and designed the work. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Ya-Lian Sa.

Ethics declarations

Ethics approval and consent to participate

This experimental protocol was established, according to the Helsinki Declaration and was approved by the Medical Ethics Committee of Yunnan Provincial First People’s Hospital (No.KHLL-2011–02). Written informed consent was obtained from all of the adult participants or the guardians of subjects younger than 18 years old.

Consent for publication

We obtained the written informed consents for publication from all the participants. Written consent was obtained from all the participants and for those younger than 18 years old, obtained from their guardians.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Figure S1.

The chromatograms of the c.919-2A>G and c.2168A>G variant in SLC26A4 gene of Sanger sequencing. A Homozygote. B Heterozygote. C Wild type.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, YQ., Ma, H., Wang, QY. et al. Low frequency of SLC26A4 c.919-2A > G variant among patients with nonsyndromic hearing loss in Yunnan of Southwest China. BMC Med Genomics 17, 55 (2024). https://doi.org/10.1186/s12920-024-01829-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12920-024-01829-3

Keywords

BMC Medical Genomics

ISSN: 1755-8794

Contact us