203例非综合征型耳聋患儿耳聋基因突变分析
Journal: Basic Medical Theory Research DOI: 10.12238/bmtr.v6i3.7518
Abstract
目的：分析湖南省郴州市非综合征型耳聋(NSHL)患儿常见耳聋基因筛查及耳聋基因panel测序结果,为本地区耳聋防控及遗传咨询提供参考。方法：选取2019年至2022年12月期间于郴州市第一人民医院确诊为双耳重度极重度非综合征型耳聋患儿203例为研究对象,采用联合探针锚定聚合测序法,针对常见22个耳聋基因的159个突变位点进行初筛,然后对筛查结果阴性或单杂和突变携带者进行218个耳聋基因panel检测。结果：203例NSHL患者经初步筛查共检出GJB2基因突变50例,SLC26A4基因突变23例,线粒体DNA12SrRNA基因突变5例,双基因携带2例,确诊48例受检者为遗传性耳聋；24例受检者进行了耳聋基因panel二次检测,检测新增GJB2基因致病突变9例,POU3F4基因致病突变1例,检测其他致病基因MYO7A、COL4A6、POU3F4、DLAPH3、TECTA、DMXL2,确诊10例受检者为遗传性聋。初筛及复筛累计检出9个致聋基因,其中GJB2及SLC26A4基因最常见,检出率分别达28.57%(58/203)、11.82%(24/203),其他依次为MT-RNR1(2.46%)、MYO7A(1.97%)、COL4A6(0.99%)、POU3F4(0.49%)、DLAPH3(0.49%)、TECTA(0.49%)、DMXL2(0.49%)。结论：GJB2及SLC26A4基因是郴州市NSHL患者最常见的耳聋突变基因,c.109G＞A位点检出率较高,应将其纳入郴州地区热点突变初筛范畴,以进一步提高初筛的阳性检出率。对初筛检测阴性或单杂合突变患者,应进行耳聋基因panel检测,以明确病因。
Keywords
非综合征型耳聋；遗传性耳聋；高通量测序
Funding
郴州市技术创新引导项目(lcyl2021067)。
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[3] YUAN Y, LI Q, SU Y, et al. Comprehensive genetic testing of Chinese SNHL patients and variants interpretation using ACMG guidelines and ethnically matched normal controls [J]. Eur J Hum Genet,2020, 8(2) :231-243.
[4] KOOHIYAN M. Genetics of Hereditary Hearing Loss in the Middle East: A Systematic Review of the Carrier Frequency of the GJB2 Mutation (35delG)[J].Audiology& neuro-otolo gy,2019,24(4).
[5] PARZEFALL T, LUCAS T, KOENIGHOFER M, et al. The role of alternative GJB2 transcription in screening for neonatal sensorineural deafness in Austria[J]. Acta Oto-laryngologica, 2017,137(4):356-360.
[6] Küçük K H, ALTUNTAS EE, Yıldırım ME, et al. The Ana lysis of GJB2, GJB3, and GJB6 Gene Mutations in Patients with Hereditary Non-Syndromic Hearing Loss Living in Sivas. J Int Adv Otol.2019Dec;15(3):373-378.
[7] 胡鹏,邓忠,谭东辉,等.湖南郴州非综合征型聋患者GJB2、SLC26A4和线粒体DNA12SrRNA基因突变分析[J].听力学及言语疾病杂志,2012,20(1):12-16.
[8] 张艳红,李娟娟,曾宪海.耳聋基因panel在耳聋基因诊断中的临床应用[J].山东大学耳鼻喉眼学报,2022,36(04):27-34.
[9] FUKUNAGA I,SHIGA T,CHENG C,et al.Generation of the ind uced pluripotent stem cell (hiPSC) line (JUFMDOi004-A) from a patient with hearing loss carrying GJB2 (p.V37I) mutation[J].Stem Cell Research,2020,43.
[10] JIANG Y, HUANG S, ZHANG Y, et al. Evolutionary origin of pathogenic GJB2 alleles in China[J].Clin Genet. 2022 Oct;102(4):305-313.
[11] DU Y,HUANG L,CHENG X,etal.Analysis of p.V37I compound heterozygous mutations in the GJB2 gene in Chinese infants and youngchildren[J].Bioscience Trends,2016,10(3):220-226.
[12] 徐梦洁,张昊晴,李彩云,等.郴州市11055名育龄女性常见遗传性耳聋基因筛查结果分析[J].中华耳科学杂志,2020,18(02):328-333.
[13] 侯小娟,丁伟,张伦,等.新疆地区795例非综合征性耳聋患者A1555G和C1494T突变分析[J].实用预防医学,2019,26(3):333-335.
[14] BOCHER S,TAI FWJ,DELMAGHANI S,etal.Ultrarare hetero zygous pathogenic variants of genes causing dominant forms of early-onset deafness underlie severe presbycusis[J].Proc Natl Acad Sci USA,2020,117(49):31278-31289.
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[16] DU W, HAN MK, WANG DY, etal. A POU3F4 mutation causes nonsyndromic hearing loss in a Chinese X-linked recessive fam iy[J].Chinese medical journal,2017,130(1):88-92.
[17] CORVINO V,APISA P,MALESCI R,etal.X-Linked Sensorineu ral HearingLoss:A Literature Review[J].Curr Genomics.2018 Aug;19(5):327-338.
[18] HUANG B, ZENG J, YUAN Y, etal.A novel mutation in POU 3F4 in a Chinese family with X-linked non-syndromic hearing loss[J].Journal of otology,2015,10(2):78-82.
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