非综合征型耳聋临床表型与GJB2基因型的关系分析

发布时间：2018-05-20 03:15

本文选题：非综合征型耳聋 + 临床表型　；参考：《中国人民解放军医学院》2014年博士论文

【摘要】：目的研究非综合征型耳聋病例的临床表型特点；分析GJB2耳聋基因在不同表型人群中的等位基因频率；分析GJB2耳聋患者（双等位基因突变）的临床表型与基因型关系；研究GJB2基因c.109GA突变和c.79GA+341AG突变的临床表型特点。方法分别对我院门诊1481例非综合征型耳聋病例的临床表型、GJB2基因突变在不同临床表型的等位基因频率检出情况、190例GJB2耳聋患者（双等位基因突变）的临床表型、GJB2基因c.109GA突变和c.79GA+341AG突变的临床表型特点进行统计学分析。结果 1.NSHL一般资料研究分析：NSHL患者多为双侧对称性感音神经性聋，发病年龄主要集中在婴幼儿期（50.08%），听力图以斜坡型(50.1%)最常见，中频U型最少（1.28%）。NSHL耳聋程度以极重度（43.21%）、中度（27.62%）及重度（22.42%）为主。37.74%的NSHL患者伴内耳畸形。 2.GJB2基因等位基因频率的结果分析：GJB2基因致病性突变等位基因频率为20.57%。最常见的致病性突变为c.235delC（11.84%），其次为c.109GA（3.75%）和c.299delAT（2.56%），再次为c.176del16bp（0.81%）。婴幼儿时发病（等位基因频率29.34%）、双耳（等位基因频率21.19%）、对称性（等位基因频率43.52%）、听力图为残余型（等位基因频率25.66%）或平坦型（等位基因频率27.13%）、无内耳畸形（等位基因频率29%）的非综合征耳聋患者GJB2基因等位基因频率高。 3．GJB2耳聋患者（双等位基因突变）的临床表型：GJB2双等位基因突变率为16.18%，其中GJB2纯合突变率为8.43%，复合杂合突变7.75%。多数表现为婴幼儿发病（77.9%）、双耳（100%）、对称性（80%）、极重度（46.84%）感音神经性耳聋患者，听力曲线为斜坡型（41.05%）多见，可出现上升型听力图（2.1%）。GJB2双等位基因听阈与发病年龄相关，与发病时间、内耳是否畸形无关。截断性突变听力损失较重。与阴性组比较，GJB2双等位基因表型特点为婴幼儿发病多见、内耳发育多正常、听力损害重、非进行性双耳感音神经性聋。与单等位基因突变组比较，GJB2双等位基因表型特点仅为婴幼儿发病、内耳畸形率低。 4、GJB2基因c.109GA和c.79GA+341AG突变的临床表型。（1）c.109GA突变:纯合突变率为0.77%（9/1174），c.109GA/其他致病性突变率为1.19%（14/1174），c.109GA单杂合突变率为4.77%（56/1174）。c.109GA纯合突变听阈均值仅为58.61dB，c.109GA/其他致病性突变患者听阈均值为72.32dB。c.109GA双等位基因突变患者在发病年龄、就诊年龄、发病时间、内耳畸形等临床表型方面与GJB2双等位基因突变特点相似。但在听力损害方面，c.109GA突变致病能力较其他致病性突变弱，更接近于无致病性突变。（2）c.79GA+341AG突变: c.79GA+341AG纯合突变双等位基因突变率为5.88%。c.79GA+341AG纯合突变患者在发病年龄、就诊年龄、发病时间、内耳畸形等临床表型方面均与阴性组无统计学差异。结论 NSHL患者临床表型多样，多为婴幼儿期发病的进展性感音神经性聋。GJB2基因突变患者表型多样，建议对所有NSHL患者进行GJB2基因检测。GJB2双等位基因表型仅婴幼儿发病多见、内耳畸形率低为其特征。c.109GA双等位基因突变患者在发病年龄、就诊年龄、发病时间、内耳畸形等临床表型方面与GJB2双等位基因突变特点相似。但在听力损害方面，，c.109GA突变致病能力较其他致病性突变弱，更接近于无致病性突变。c.79GA+341AG纯合突变患者临床表型方面与阴性组相似。
[Abstract]:objective
To study the clinical phenotypic characteristics of non syndromic deafness cases, analyze the allele frequency of GJB2 deafness gene in different phenotypic populations, analyze the relationship between the clinical phenotype and genotype of GJB2 deafness (double allele mutation), and study the clinical phenotypic characteristics of the c.109GA mutation of the GJB2 gene and the c.79GA+ 341AG mutation.
Method
The clinical phenotype of 1481 cases of non syndromic deafness in our hospital, the detection of allelic frequency of GJB2 gene mutation in different clinical phenotypes, the clinical phenotypes of 190 cases of GJB2 deafness (double allele mutation), the c.109GA mutation of GJB2 gene and the clinical phenotypic characteristics of c.79GA+341AG process were statistically analyzed.
Result
1.NSHL general data study analysis: NSHL patients are mostly bilateral symmetrical sensorineural deafness, the age of onset mainly concentrates in infantile period (50.08%), the most common hearing map is slope type (50.1%), and the least (1.28%).NSHL deafness (43.21%), moderate (27.62%) and severe (22.42%).37.74% of NSHL patients with internal ear malformation. Shape.
The analysis of the frequency of 2.GJB2 allele: the most common pathogenicity mutation of the GJB2 gene mutation allele was c.235delC (11.84%), followed by c.109GA (3.75%) and c.299delAT (2.56%), and again c.176del16bp (0.81%). The incidence of allele (allele frequency 29.34%) in infants and infants (allele frequency 21.19%). Symmetries (allele frequency 43.52%), audition (allele frequency 25.66%) or flat type (allele frequency 27.13%), and non syndromic deafness (allele frequency 29%) of non syndromic deafness were high in the GJB2 allele.
The clinical phenotype of 3.GJB2 deafness (double allele mutation): the GJB2 double allele mutation rate was 16.18%, of which the GJB2 homozygous mutation rate was 8.43%, and the complex heterozygous mutation 7.75%. was mostly found in infants (77.9%), binaural (100%), symmetry (80%), and extreme weight (46.84%) sensorineural deafness, and the hearing curve was slope type (41.05%). (2.1%) the rise type audiometry (2.1%) the hearing threshold of the double allele is related to the age of the onset of the disease. It is not related to the time of the onset and the malformation of the inner ear. The hearing loss of the truncated mutation is heavier. Compared with the negative group, the phenotype characteristics of the GJB2 double allele are more common in infants and infants, the internal ear development is more normal, the hearing loss is heavy, and the non progressive binaural sense is found. Compared with the single allele mutation group, the phenotype of GJB2 double alleles was only infantile onset, and the rate of inner ear deformity was low.
4, the clinical phenotype of GJB2 gene c.109GA and c.79GA+341AG mutations.
(1) c.109GA mutation: the homozygous mutation rate was 0.77% (9/1174), the other pathogenicity mutation rate of c.109GA/ was 1.19% (14/1174), the single heterozygous mutation rate of c.109GA was 4.77% (56/1174).C.109GA homozygous hearing threshold value only 58.61dB, and the auditory threshold value of c.109GA/ other pathogenic mutation patients was 72.32dB.c.109GA double allele mutation patients at the age of onset. The clinical phenotypes such as age, onset time, and internal ear malformation were similar to those of GJB2 double allele, but in hearing impairment, the c.109GA mutation was weaker than other pathogenic mutations, and was closer to no pathogenic mutation.
(2) c.79GA+341AG mutation: c.79GA+341AG homozygous mutant double allele mutation rate of 5.88%.c.79GA+341AG homozygous mutation patients at the onset age, age, onset time, internal ear malformation, and other clinical phenotypes were not statistically different from those in the negative group.
conclusion
The clinical phenotype of NSHL patients is diverse and the phenotype of.GJB2 gene mutations in the progressive sensorineural deafness is varied. It is suggested that the GJB2 gene detection of.GJB2 double alleles in all NSHL patients is only common in infants and infants, and the low rate of inner ear malformation is the age of the patients with the characteristic.C.109GA double allele mutation. The clinical phenotypes such as age, onset time, and internal ear malformation were similar to those of GJB2 double allele, but in hearing impairment, the c.109GA mutation was weaker than other pathogenic mutations, and was similar to the negative group in the clinical phenotype of the non pathogenic.C.79GA+341AG homozygous mutation.
【学位授予单位】：中国人民解放军医学院
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R764.43

【相似文献】