Morell R J, Kim H J, Hood L J, Goforth L, Friderici K, Fisher R, Van Camp G, Berlin C I, Oddoux C, Ostrer H, Keats B, Friedman T B
Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD 20850, USA.
N Engl J Med. 1998 Nov 19;339(21):1500-5. doi: 10.1056/NEJM199811193392103.
Mutations in the GJB2 gene cause one form of nonsyndromic recessive deafness. Among Mediterranean Europeans, more than 80 percent of cases of nonsyndromic recessive deafness result from inheritance of the 30delG mutant allele of GJB2. We assessed the contribution of mutations in GJB2 to the prevalence of the condition among Ashkenazi Jews.
We tested for mutations in GJB2 in DNA samples from three Ashkenazi Jewish families with nonsyndromic recessive deafness, from Ashkenazi Jewish persons seeking carrier testing for other conditions, and from members of other ethnic groups. The hearing of persons who were heterozygous for mutations in GJB2 was assessed by means of pure-tone audiometry, measurement of middle-ear immittance, and recording of otoacoustic emissions.
Two frame-shift mutations in GJB2, 167delT and 30delG, were observed in the families with nonsyndromic recessive deafness. In the Ashkenazi Jewish population the prevalence of heterozygosity for 167delT, which is rare in the general population, was 4.03 percent (95 percent confidence interval, 2.5 to 6.0 percent), and for 30delG the prevalence was 0.73 percent (95 percent confidence interval, 0.2 to 1.8 percent). Genetic-linkage analysis showed conservation of the haplotype for 167delT but the existence of several haplotypes for 30delG. Audiologic examination of carriers of the mutant alleles who had normal hearing revealed subtle differences in their otoacoustic emissions, suggesting that the expression of mutations in GJB2 may be semidominant.
The high frequency of carriers of mutations in GJB2 (4.76 percent) predicts a prevalence of 1 deaf person among 1765 people, which may account for the majority of cases of nonsyndromic recessive deafness in the Ashkenazi Jewish population. Conservation of the haplotype flanking the 167delT mutation suggests that this allele has a single origin, whereas the multiple haplotypes with the 30delG mutation suggest that this site is a hot spot for recurrent mutations.
GJB2基因的突变会导致一种非综合征性隐性耳聋。在地中海欧洲人中，超过80%的非综合征性隐性耳聋病例是由GJB2基因30delG突变等位基因的遗传所致。我们评估了GJB2基因突变对阿什肯纳兹犹太人中该病患病率的影响。
我们对来自三个患有非综合征性隐性耳聋的阿什肯纳兹犹太家庭、寻求其他疾病携带者检测的阿什肯纳兹犹太人以及其他种族群体成员的DNA样本进行了GJB2基因突变检测。通过纯音听力测定、中耳声导抗测量和耳声发射记录来评估GJB2基因突变杂合子个体的听力。
在患有非综合征性隐性耳聋的家庭中观察到GJB2基因的两个移码突变，即167delT和30delG。在阿什肯纳兹犹太人群体中，167delT杂合子的患病率在普通人群中较为罕见，为4.03%（95%置信区间为2.5%至6.0%），30delG的患病率为0.73%（95%置信区间为0.2%至1.8%）。基因连锁分析显示167delT的单倍型具有保守性，但30delG存在几种单倍型。对听力正常的突变等位基因携带者进行的听力学检查显示，他们的耳声发射存在细微差异，这表明GJB2基因突变的表达可能是半显性的。
GJB2基因突变携带者的高频率（4.76%）预示着每1765人中会有1名耳聋患者，这可能是阿什肯纳兹犹太人群体中大多数非综合征性隐性耳聋病例的原因。167delT突变侧翼单倍型的保守性表明该等位基因有单一起源，而30delG突变的多种单倍型表明该位点是复发性突变的热点。
