Jun A I, McGuirt W T, Hinojosa R, Green G E, Fischel-Ghodsian N, Smith R J
Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City 52242, USA.
Laryngoscope. 2000 Feb;110(2 Pt 1):269-75. doi: 10.1097/00005537-200002010-00016.
Mutations in GJB2, a gene that encodes a gap junction protein, Connexin 26 (Cx26), are responsible for approximately one third of sporadic severe-to-profound or profound congenital deafness and half of severe-to-profound or profound autosomal recessive nonsyndromic hearing loss (ARNSHL). Mouse mutants homozygous for knockouts of this gene are nonviable, precluding histopathologic studies of the associated inner ear pathology in this animal model. Therefore, we studied archival temporal bone sections to identify temporal bone donors with Cx26-related deafness.
Temporal bone donors with a history of congenital severe-to-profound or profound deafness were identified in the registry of the Temporal Bone Library at the University of Iowa. Histological findings were interpreted in a blinded fashion. DNA extracted from two celloidin-embedded mid-modiolar sections from each temporal bone was screened for the 35delG Cx26 mutation. The entire coding region of Cx26 was screened for other deafness-causing mutations if the 35delG mutation was detected.
Of five temporal bone donors with congenital severe-to-profound deafness, one donor was found to have Cx26-related deafness. This individual was a Cx26 compound heterozygote, carrying the 35delG mutation and a noncomplementary Cx26 missense mutation on the opposing allele. Microscopic evaluation of this temporal bone showed no neural degeneration, a good population of spiral ganglion cells, near-total degeneration of hair cells in the organ of Corti, a detached and rolled-up tectorial membrane, agenesis of the stria vascularis, and a large cyst in the scala media in the region of the stria vascularis.
This study is the first to report the temporal bone histopathology associated with Cx26-related deafness. Preservation of neurons in the spiral ganglion suggests that long-term successful habilitation with cochlear implants may be possible in persons with severe-to-profound or profound Cx26-related deafness.
编码缝隙连接蛋白连接蛋白26（Cx26）的GJB2基因突变，约占散发性重度至极重度或极重度先天性耳聋的三分之一，以及重度至极重度或极重度常染色体隐性非综合征性听力损失（ARNSHL）的一半。该基因敲除的纯合子小鼠突变体无法存活，这使得在此动物模型中对相关内耳病理学进行组织病理学研究变得不可能。因此，我们研究了存档的颞骨切片，以识别患有Cx26相关耳聋的颞骨供体。
在爱荷华大学颞骨库登记处识别出有先天性重度至极重度或极重度耳聋病史的颞骨供体。以盲法解读组织学结果。从每个颞骨的两个火棉胶包埋的中轴螺旋切片中提取的DNA，筛查35delG Cx26突变。如果检测到35delG突变，则对Cx26的整个编码区进行其他致聋突变的筛查。
在五名患有先天性重度至极重度耳聋的颞骨供体中，发现一名供体患有Cx26相关耳聋。该个体是Cx26复合杂合子，携带35delG突变以及相对等位基因上的一个非互补Cx26错义突变。对该颞骨的显微镜评估显示无神经退变，螺旋神经节细胞数量良好，柯蒂器中的毛细胞几乎完全退变，盖膜分离并卷曲，血管纹发育不全，以及血管纹区域的中阶有一个大囊肿。
本研究首次报告了与Cx26相关耳聋相关的颞骨组织病理学。螺旋神经节中神经元的保留表明，重度至极重度或极重度Cx26相关耳聋患者长期成功使用人工耳蜗进行康复训练可能是可行的。
