CAJ | 학술논문

　　目的分析非综合征性耳聋患儿的致聋基因和携带SLC26A4基因突变者的临床表现、康复设备使用及康复教育机构的选择情况。方法对195例非综合征性耳聋患儿进行耳聋基因芯片筛查。对34例携带SLC26A4基因突变的耳聋患儿进行了进一步的测序分析，并对这些聋儿进行病史和听力学检查回顾性分析以及康复设备使用和康复教育机构选择的随访。结果①在195例耳聋患者中，基因芯片检测出的遗传性耳聋比率为43.59%，其中GJB2、SLC26A4致病突变的携带率分别为24.10%、17.44%。②在34例携带SLC26A4基因突变的耳聋患者中，芯片检测出纯合或者复合杂合突变者13例。通过随后的测序方法，在15例SLC26A4基因单杂合突变患者中检出第二个致病突变位点，诊断为复合杂合突变患者。这34名患儿中，中度耳聋3人，重度耳聋12人，极重度耳聋19人；听力波动者10人，没有明显波动者24人；27人选择了助听器，7人进行了人工耳蜗手术。28例SLC26A4基因纯合或者复合杂合突变患者中，前庭水管扩大者20人，1人正常，7人没有接受CT检查。③34名携带SLC26A4基因突变的聋儿中，3～6岁者共19人，其中13人选择了康复中心，3人选择了普通幼儿园，3人选择了家庭康复。6岁以上者15人，13人选择了普通小学，2人选择了聋校。结论①结果表明，遗传因素是儿童耳聋的重要致病原因，GJB2和SLC26A4是两个主要的致病基因。②测序和芯片联合的方法可以增加SLC26A4突变致聋的诊断率。③在3～10岁年龄段，91.18%的SLC26A4基因突变患儿为重度-极重度耳聋，听力无明显波动者多于听力波动者，影像学多显示为前庭水管扩大。④康复中心和普通小学是携带SLC26A4基因突变的耳聋儿童最常选择的康复教育机构。
　　목적분석비종합정성이롱환인적치롱기인화휴대SLC26A4기인돌변자적림상표현、강복설비사용급강복교육궤구적선택정황。방법대195례비종합정성이롱환인진행이롱기인심편사사。대34례휴대SLC26A4기인돌변적이롱환인진행료진일보적측서분석，병대저사롱인진행병사화은역학검사회고성분석이급강복설비사용화강복교육궤구선택적수방。결과①재195례이롱환자중，기인심편검측출적유전성이롱비솔위43.59%，기중GJB2、SLC26A4치병돌변적휴대솔분별위24.10%、17.44%。②재34례휴대SLC26A4기인돌변적이롱환자중，심편검측출순합혹자복합잡합돌변자13례。통과수후적측서방법，재15례SLC26A4기인단잡합돌변환자중검출제이개치병돌변위점，진단위복합잡합돌변환자。저34명환인중，중도이롱3인，중도이롱12인，겁중도이롱19인；은력파동자10인，몰유명현파동자24인；27인선택료조은기，7인진행료인공이와수술。28례SLC26A4기인순합혹자복합잡합돌변환자중，전정수관확대자20인，1인정상，7인몰유접수CT검사。③34명휴대SLC26A4기인돌변적롱인중，3～6세자공19인，기중13인선택료강복중심，3인선택료보통유인완，3인선택료가정강복。6세이상자15인，13인선택료보통소학，2인선택료롱교。결론①결과표명，유전인소시인동이롱적중요치병원인，GJB2화SLC26A4시량개주요적치병기인。②측서화심편연합적방법가이증가SLC26A4돌변치롱적진단솔。③재3～10세년령단，91.18%적SLC26A4기인돌변환인위중도-겁중도이롱，은력무명현파동자다우은력파동자，영상학다현시위전정수관확대。④강복중심화보통소학시휴대SLC26A4기인돌변적이롱인동최상선택적강복교육궤구。
Objective To investigate the molecular etiologic causes of pediatric sporadic non-syndromic hearing loss and to analyze the clinical symptoms and choices of rehabilitation and educational places in hearing-impaired children with SLC26A4 mutations. Methods 195 Chinese children with sporadic non-syndromic hearing loss were selected for microarray-based mutation detection of nine hot spot mutations in four of the most common deafness-related genes (GJB2, SLC26A4, GJB3 and 12S rRNA). Of these, 34 patients with SLC26A4 mutations detected by microarray were subjected to further sequencing analysis of the whole SLC26A4 coding region in order to confirm the microarray results and to identify a possible second mutant allele for those with one SLC26A4 mutation. Case history,hearing level and choices of rehabilitation and educational places were surveyed in children with SLC26A4 mutations. Results (1)The incidence of genetic causes was 43.59% in 195 children with sporadic non-syndromic hearing loss. Among them, 24.10% of cases were caused by GJB2 mutations and 17.44% of cases were caused by SLC26A4 mutations. (2)A total of 34 children (17.44%) were found to be carrying mutant SLC26A4 sequences using microarray methods. According to microarray results,13 children carried two mutant alleles of SLC26A4 and 21 children carried one mutant allele of SLC26A4. With further sequencing analysis, additional 15 of the 21 patients previously thought to have monoallelic mutations were diagnosed as compound heterzygotes. 31 children with SLC26A4 mutations presented with severe to profound sensorineural hearing loss. Hearing loss was fluctuating and progressive in 29.41% of these cases.Among the 34 children with SLC26A4 mutations,27 chose hearing aids and 7 received cochlear implantation.For the 28 patients with homozygous or compound heterozygous mutations in SLC26A4 genes,20 had large vestibular aqueduct, 1 was normal according to the CT results and 7 didn't receive the CT scans. (3)For the 19 children between 3 to 6 years old, 13 of them chose the rehabilitation centers 3 children chose regular daycares and 3 children chose family rehabilitation. For the 15 children over 6 years old, 13 of them went to regular primary schools and 2 children went to schools for the deaf. Conclusion ① The results demonstrated that genetic factors were important causes for sporadic non-syndromic hearing loss in children. Mutations of GJB2 and SLC26A4 are two major causes for genetic hearing loss.②The combination of microarray testing and sequencing analysis is thus a useful and high-throughput method for the diagnosis of genetic hearing loss.③ For the hearing-impaired children between 3 to 10 years old, over 91% of children with SLC26A4 mutations have severe to profound hearing loss, and children with fluctuating hearing loss are less than those with stable hearing loss. Most of them have large vestibular aqueduct in the CT images.④ The rehabilitation centers and primary schools are the first choices for the rehabilitation of the children with mutations in the SLC26A4 genes.