Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect:: implications for genetic counselling
Clinical features of the prevalent form of childhood deafness, DFNB1, due to a connexin-26 gene defect:: implications for genetic counselling
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DOI：
10.1016/s0140-6736(98)11071-1
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发表时间：
1999-04-17
期刊：
影响因子：
168.9
通讯作者：
Petit, C
中科院分区：
文献类型：
--
作者：
Denoyelle, F;Marlin, S;Petit, C
背景DFNB 1是一种常染色体隐性遗传性耳聋，是人类最常见的遗传性疾病之一。迄今为止，没有DFNB 1内耳缺陷的临床特征已被报道，这排除了提供预后信息和遗传consultations.Methods方法，我们参加了一项前瞻性研究，140名儿童从104个家庭的感音神经性耳聋与不同程度的听力损失。这些儿童要么属于常染色体隐性遗传性耳聋（DFNB）家族，要么是散发病例。我们在CX 26的5'非编码外显子和编码区中寻找突变。结果：在88个语前聋家系中，有43个家系（49%）存在CX 26突变，而在16个语后聋家系中，无一例存在CX 26突变（P < 0 . 05）。01）。对54例CX 26双等位基因突变的语前聋儿童和57例无CX 26突变的语前聋儿童的内耳缺陷进行比较。DFNB 1耳聋从轻度到重度不等，与倾斜或平坦的听力曲线和放射学正常的内耳相关。听力损失是不进行性的16例中的11个测试，并在兄弟姐妹之间的耳聋的严重程度的变化是common.Interpretation-特征性的听力和放射学特征DFNB 1应用于指导调查的参考，CX 26分子诊断测试，聋哑儿童的兼容表型。现在可以向家庭提供预后信息：DFNB 1耳聋的听力损失在大多数情况下是非进行性的，至少到成年早期。遗传咨询的一个重要因素是，由于DFNB 1导致的听力损失的严重程度是极其可变的，即使在家庭中也无法预测。
Background DFNB1, the locus of an autosomal recessive form of deafness due to mutations in the connexin-26 gene (CX26 or GJB2) is one of the most frequent hereditary defects in human beings. To date, no clinical characterisation of the DFNB1 inner-ear defects has been reported, which precludes the provision of prognostic information and genetic counselling.Methods We enrolled, in a prospective study, 140 children from 104 families affected by sensorineural deafness with various degrees of hearing loss. The children either belonged to a family affected by autosomal recessive deafness (DFNB family) or represented sporadic cases. We searched for mutations in the 5' non-coding exon and in the coding region of CX26. Audiometric and radiological features were investigated and compared in deaf children with and without CX26 mutations.Findings CX26 mutations were present in 43 (49%) of the 88 families with cases of prelingual deafness versus none of;the 16 families with postlingual forms of deafness (p < 0 . 01). The inner-ear defects of 54 prelingually deaf children with biallelic CX26 mutations were compared with the defects in 57 prelingually deaf children without CX26 mutations. DFNB1 deafness varied from mild to profound, associated with sloping or flat audiometric curves and a radiologically normal inner ear. Hearing loss was not progressive in 11 of 16 cases tested, and variations in the severity of deafness between siblings were common.Interpretation The characteristic audiometric and radiological features of DFNB1 should be the reference used to guide the investigation,by CX26 molecular diagnostic tests,of deaf children with a compatible phenotype. Prognostic information can now be given to families: the hearing loss in DFNB1 deafness is non-progressive in most cases, at least up to young adulthood. An important element for genetic counselling is that the severity of hearing loss due to DFNB1 is extremely variable and cannot be predicted, even within families.