Ravecca Francesca, Berrettini Stefano, Forli Francesca, Marcaccini Mirella, Casani Augusto, Baldinotti Fulvia, Fogli Antonella, Siciliano Gabriele, Simi Paolo
Neuroscience Department, University of Pisa, Pisa, Italy.
J Otolaryngol. 2005 Apr;34(2):126-34. doi: 10.2310/7070.2005.04017.
The present study evaluated the frequency and type of mutations throughout the entire GJB2 region in a population of 39 patients affected with sporadic progressive "idiopathic" hearing loss.
A large series of patients suffering from progressive hearing loss underwent a systematic screening program to identify the etiology of the hearing loss. Of these patients, 39 presented with sporadic idiopathic progressive hearing loss and were included in this study.
We performed molecular analysis of GJB2 in each patient sequencing the genomic deoxyribonucleic acid (DNA) in both directions for detection of GJB2 mutations. Furthermore, in all patients bearing a Cx26 mutation, a search was also conducted for mutations or deletions of GJB6 (Cx30 gene) and for the A1555G mutation of the mitochondrial DNA. A control group was also considered to evaluate the frequency of Cx26 mutations in the normal population.
A Cx26 gene mutation was detected in nine cases. One subject was found to bear a homozygous genotype for the 35delG mutation, another subject was compound heterozygous for 35delG and E47X, and the remaining patients showed heterozygous genotypes (35delG, L90P, R127H, M34T, V153I, V37I). No mutation or delection of the Cx30 gene was observed in these nine patients, and none of them presented with the A1555G mutation in the mitochondrial DNA. In the control group (40 individuals), a Cx26 mutation was detected in two cases (5%).
About 23% of our patients (nine subjects) presented with mutations in GJB2, and 18% (seven subjects) were heterozygous. However, most of the described mutations are recessive, so a monogenic model of inheritance cannot explain the deafness phenotype. On the basis of these findings, we can speculate that the heterozygote Cx26 genotype could be a cause of progressive hearing loss, probably in association with mutations in other alleles. Thus, we recommend carefully following all hearing-impaired subjects with GJB2 mutations, even if they present with only mild hearing loss, because the hearing deficit could worsen. Furthermore, molecular analysis of the Cx26 gene should also be performed in adult patients affected with idiopathic progressive hearing loss.
本研究评估了39例散发型进行性“特发性”听力损失患者整个GJB2区域的突变频率和类型。
一大组进行性听力损失患者接受了系统的筛查程序，以确定听力损失的病因。在这些患者中，39例表现为散发性特发性进行性听力损失，并被纳入本研究。
我们对每位患者的GJB2进行了分子分析，双向测序基因组脱氧核糖核酸（DNA）以检测GJB2突变。此外，在所有携带Cx26突变的患者中，还搜索了GJB6（Cx30基因）的突变或缺失以及线粒体DNA的A1555G突变。还设立了一个对照组来评估正常人群中Cx26突变的频率。
9例检测到Cx26基因突变。1例为35delG突变的纯合基因型，另1例为35delG和E47X的复合杂合子，其余患者表现为杂合基因型（35delG、L90P、R127H、M34T、V153I、V37I）。这9例患者均未观察到Cx30基因的突变或缺失，且均未出现线粒体DNA的A1555G突变。在对照组（40人）中，2例（5%）检测到Cx26突变。
约23%的患者（9例）存在GJB2突变，18%（7例）为杂合子。然而，大多数所描述的突变是隐性的，因此单基因遗传模式无法解释耳聋表型。基于这些发现，我们推测杂合子Cx26基因型可能是进行性听力损失的一个原因，可能与其他等位基因的突变有关。因此，我们建议对所有携带GJB2突变的听力受损患者进行密切随访，即使他们仅表现为轻度听力损失，因为听力缺陷可能会恶化。此外，对于患有特发性进行性听力损失的成年患者，也应进行Cx26基因的分子分析。
