目的 分析非综合征型耳聋患儿的GJB2、SLC26A4基因和线粒体12S rRNA突变频率，扩充中国人群常见耳聋基因突变流行病学数据，为发展适合的聋病基因筛查提供数据基础。方法 收集220名散发非综合征型耳聋病例的外周血样本和临床资料;应用聚合酶链反应(PCR)和直接测序，对患者和150例正常对照进行GJB2、SLC26A4基因和线粒体12S rRNA突变检测。结果 1)220例患者中146(66.36%)例患者携带至少1个GJB2基因突变，35(15.91%)例患者携带至少1个SLC26A4基因突变，3(1.36%)例为线粒体A1555G突变。正常对照中3(2%)例携带GJB2致病突变。2)GJB2基因c.235delC(19.32%)突变是最常见的致病突变，其次是SLC26A4基因IVS7-2A>G(9.09%)突变。3)检出的36种突变中，包括2种GJB2和1种SLC26A4新突变。结论 本研究扩充了GJB2基因、SLC26A4基因和线粒体DNA A1555G突变在中国人群中的基因突变数据，并发现了3种新的突变，为分子诊断和扩展聋病基因筛查提供数据参考。
Abstract
Objective To examine the mutation frequencies of deafness genes GJB2,SLC26A4,and mitochondrial DNA(mtDNA) 12S rRNA in children associated with non-syndromic hearing loss,and to expand data base of mutation in Chinese,for development of optimal genetic screening services for hearing impairment. Methods Blood samples and clinical data of 220 sporadic cases with non-syndromic hearing loss and 150 normal controls were collected.The GJB2,SLC26A4,and mtDNA 12S rRNA gene of the patients and normal controls were amplified by polymerase chain reaction(PCR),then subjected to automatic DNA sequencing. Results Analysis revealed that 146(66.36%) and 35(15.91%) of 220 patients with hearing loss carried at least 1 mutant allele in GJB2 and SLC26A4 respectively,and 3(1.36%) patients carried mtDNA A1555G mutations.Overall 36 mutations were detected in this cohort of patients,including 2 novel mutations in GJB2 and 1 novel mutation in SLC26A4 respectively.GJB2 gene c.235delC(19.32%)and SLC26A4 gene IVS7-2A>G(9.09%) were the most common pathogenic mutation.3(2%) of 150 normal control carried pathogenic mutations in GJB2 gene. Conclusion This research demonstrated that a high prevalence of GJB2,SLC26A4,and mtDNA A1555G mutations in Chinese children with non-syndromic hearing loss,and expanded data base of common gene of deafness,and discovered 3 novel mutations,which provided basic information for the molecular diagnosis and gene screening of deafness.
关键词
非综合征型耳聋 /
GJB2 /
SLC26A4 /
线粒体12S rRNA /
突变
Key words
non-syndromic hearing loss /
GJB2 /
SLC26A4 /
mitochondrial 12S rRNA /
mutation
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参考文献
[1] Bitner-Glindzicz M.Hereditary deafness and phenotyping in humans[J].Br Med Bull,2002,63:73-94.
[2] Wang QJ,Zhao YL,Rao SQ,et al.Newborn hearing concurrent gene screening can improve care for hearing loss:a study on 14,913 Chinese newborns[J].Int J Pediatr Otorhinolaryngol,2011,75:535-542.
[3] Smith RJH,Bale JF,White KR.Sensorineural hearing loss in children[J].Lancet,2005,365:879-890.
[4] Ouyang XM,Yan D,Yuan HJ,et al.The genetic bases for non-syndromic hearing loss among Chinese[J].J Hum Genet,2009,54:131-140.
[5] Yuan Y,You Y,Huang D,et al.Comprehensive molecular etiology analysis of nonsyndromic hearing impairment from typical areas in China[J].J Transl Med,2009,7:79-90.
[6] Dai P,Yu F,Han B,et al.GJB2 mutation spectrum in 2063 Chinese patients with nonsyndromic hearing impairment[J].J Transl Med,2009,7:1-12.
[7] Yuan Y,Yu F,Wang G,et al.Prevalence of the GJB2 IVS1+1G > A mutation in Chinese hearing loss patients with monoallelic pathogenic mutation in the coding region of GJB2[J].J Transl Med,2010,8:127-135.
[8] Lu J,Li Z,Zhu Y,et al.Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss[J].Mitochondrion,2010,10:380-390. [9] Azaiez H,Yang T,Prasad S,et al.Genotype-phenotype correlation for SLC26A4-related deafness[J].Hum Genet,2007,122:451-460.
[10] Samanich J,Lowes C,Burk R,et al.Mutations in GJB2,GJB6,and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment[J].Am J Med Genet A,2007,143(8):830-838.
[11] Wang QJ,Zhao YL,Rao SQ,et al.A distinct spectrum of SLC26A4 mutations in patients with enlarged vestibular aqueduct in China[J].Clin Genet,2007,72(3):245-254.
[12] Coyle B,Reardon W,Herbrick JA,et al.Molecular analysis of the PDS gene in Pendred syndrome[J].Hum Mol Genet,1998,7:1105-1113.
[13] Duman D,Tekin M.Autosomal recessive nonsyndromic deafness genes:a review[J].Front Biosci,2012,17:2213-2236.
[14] Hwa HL,Ko TM,Hsu CJ,et al.Mutation spectrum of the connexin 26(GJB2) gene in Taiwanese patients with prelingual deafness[J].Genet Med,2003,5(3):161-165.
[15] 孙顺昌,刘一心,彭运生,等.遗传性非综合征型耳聋患者GJB2基因编码序列分析[J].中华医学遗传学杂志,2011,28(4):409-413.
基金
武汉市青年科技晨光计划项目(200950431210)
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