摘要
目的通过对常见致聋基因的筛查,初步了解陕西省部分耳聋人群的分子遗传病因及其特点。方法在知情同意的基础上,采集陕西地区283例非综合征型聋哑学生外周静脉血,提取基因组DNA,应用多聚酶链反应(polymerase chain reaction,PCR)扩增GJB2基因编码区、SLC26A4基因第8、第19外显子及线粒体DNA(mi-tochondria DNA,mtDNA)目的片断,Alw26Ι限制性内切酶酶切检测m1555A>G点突变,对酶切阳性标本和GJB2基因编码区及SLC26A4基因的第8、第19外显子进行DNA测序。结果 283例患者中,9例(3.18%,9/283)存在线粒体DNA12SrRNAm.1555A>G均质性突变;55例为GJB2基因突变所致(包括纯合、复合杂合或显性携带者),突变频率为19.43%(55/283),8例为GJB2基因突变携带者。c.235delC和c.299_300delAT等位基因频率分别为14.13%(80/566)和3.89%(22/566),占所有GJB2基因致病等位基因数的87.18%(102/117),是该地区的热点突变;7例为SLC26A4基因的双等位基因突变,突变频率为2.47%(7/283),13例携带SLC26A4基因单等位基因碱基改变,c.919-2A>G和c.2168A>G(p.H723R)占所有SLC26A4基因碱基改变等位基因数的88.89%(24/27)。结论 GJB2基因突变是导致陕西省聋哑学生听力损失的主要原因,c.235delC是其最常见的突变形式,c.919-2A>G和c.2168A>G(p.H723R)为SLC26A4基因主要的两种突变形式。对该地区耳聋患者行三个常见基因筛查,将为25.08%(71/283)患者提供明确分子病因学诊断,并将对32.51%(92/283)的患者及家族成员给予咨询。
Objective To understand the molecular genetic causes and their characteristics of deafness in Shanxi province, a genetic screening of three common hereditary deafness genes was setup in this province. Methods Peripheral blood samples were obtained from a total of 283 patients with non--syndromie sensorineural hearing loss from special education schools in Shanxi province to extract genomie DNA. The mitochondrial DNA 12S rRNA m. 1555A〉G mutation was screened by PCR Alw26I digestion and a sequence analysis of PCR and direct sequencing were used to analyze the coding region of GJB2 gene and exon 8 and 19 of SLC26A4 gene. Results Among 283 deaf students, 9 cases （3.18%） were found to carry mtDNA 128 rRNA m. 1555A〉G homozygous mutation, 55 cases （19.43%） were caused by GJB2 gene mutations and 7 cases （2.47%） had two mutated alleles （homozygote and compound heterozygote） of SLC26A4 gene. In detail, 22.61% （63/283） patients carried GJB2 mutations,including 8 single mutant carriers. The allele frequency of c. 235delC and c. 299_300delAT were 14. 13% （80/566） and 3.89%（22/566）, respectively, making up 87.18% （102/117） of all pathogenic mutated alleles for GJB2 gene. The single mutant allele carriers of SLC26A4 was 13, and two types （c. 919-2A〉G and c. 2168A〉G） accounted for 88.89% （24/27） mutations in total. Conclusion This genetic epidemiological study demonstrated that 25.08% （71/283） of the deaf students in Shanxi province can be detected at younger ages by genetic testing of three common hearing loss genes （GJB2, SLC26A4 and mtDNA 12S rRNA m. 1555A〉G）. As a result 32.51%（92/283） patients and family member can acquire more effective genetic counseling. GJB2 gene mutations are the main cause of deaf students in shaanxi province,and c. 235delc is its main form. c. 919-2A〉G and c. 2168A〉G（pH 723R） are the major two mutant forms of SLC26A4 gene.
出处
《听力学及言语疾病杂志》
CAS
CSCD
北大核心
2010年第3期225-228,共4页
Journal of Audiology and Speech Pathology
基金
国家863项目(2006AA02Z181)
国家自然基金重点项目(30830104)
国家自然基金面上项目(30672310
30771857&30771203)
高等学校全国优秀博士学位论文作者专项资金资助项目(200463)
国家973项目(2007CB507400)
北京市重大专项课题项目(7070002)
国家"十一五"科技支撑计划(2006BAI02B06&2007BAI18B12)
甘肃省科技厅-技术研究与开发专项机会基金课题(0805TCYA004)
甘肃省自然科学研究基金(096RJZA074)联合资助
