The phenotype of DFNA13/COL11A2:: Nonsyndromic autosomal dominant mid-frequency and high-frequency sensorineural hearing impairment
The phenotype of DFNA13/COL11A2:: Nonsyndromic autosomal dominant mid-frequency and high-frequency sensorineural hearing impairment
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DOI：
10.1016/s0196-0709(00)80006-x
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发表时间：
2000-03-01
期刊：
影响因子：
--
通讯作者：
Cremers, C
中科院分区：
文献类型：
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作者：
Kunst, H;Huybrechts, C;Cremers, C
目的：为了研究非综合征进行性感音神经性听力障碍患者的COL 11 A2突变（DFNA 13）在荷兰kindred.Study设计：调查。设置：耳鼻喉科的一所大学hospital.Patients：21个生活成员的荷兰家庭（150亲属在5代; 49人进行了研究）与常染色体显性遗传非综合征感音神经性听力障碍表现出连锁的DFNA 13位点。突变分析显示COL 11 A2基因存在错义突变。方法：收集病史，测量所有受影响者的听阈水平，并评估听力损失。仅1例病例可进行纵向分析（使用年龄阈值数据的线性回归分析）。横断面分析包括比较家庭不同世代之间的阈值水平。此外，听力阈值进行了校正的中位数老年性聋，以找出是否听力障碍的特点，这一特点是固定或进行性。前庭功能进行了评价，眼震电图，通过使用旋转和热量tests.Results：大多数受影响的人的日期，他们的第一个听力障碍症状的第二至第三个十年的生活。在病史上，4名受影响的人从幼儿期开始就有听力障碍症状。先证者（IV 26）的纵向分析显示了先天性偏移和实质性早期进展的异常组合。每个年龄组内的频率之间以及第四代和第三代（分别为30-38岁和58-74岁）覆盖的两个年龄组之间的高频（2-8 kHz）下，大多数阈值水平存在显着差异;后者可归因于老年性聋。在感音神经性听力障碍的受试者中，约有一半（8/17）的人出现了各种热量异常，包括反射消失。年龄校正后，听力障碍--可能从早期开始就存在并保持稳定--通常在1、2和6 kHz处显示出最差或次差阈值最佳或次佳阈值在0.25至0.5和4 kHz（25 dB）。据推测，老年性耳聋从40岁开始，导致典型形状的听力图改变，被描述为中频听力障碍伴额外的高频听力障碍。
Objective: To study nonsyndromic progressive sensorineural hearing impairment in patients with a COL11A2 mutation (DFNA13) in a Dutch kindred.Study Design: Survey.Setting: Department of otorhinolaryngology of a university hospital.Patients: Twenty-one living members of a Dutch family (150 relatives in 5 generations; 49 were studied) with autosomal dominant nonsyndromic sensorineural hearing impairment showed linkage to the DFNA13 locus. Mutation analysis revealed a missense mutation in the COL11A2 gene.Methods: History was taken, hearing threshold levels were measured in all affected persons, and penetrance was evaluated. Longitudinal analysis (using linear regression analysis of threshold-on-age data) was possible in only 1 case. Cross-sectional analysis comprised the comparison of threshold levels between different generations of the family. Also, hearing thresholds were corrected for median presbyacusis to find out whether the hearing impairment characteristic of this trait is stationary or progressive. Vestibular functions were evaluated with electronystagmography, by use of rotatory and caloric tests.Results: Most of the affected persons dated their first hearing impairment symptoms to the second to third decade of life. A possibly reduced penetrance was found. Anamnestically, 4 affected persons had hearing impairment symptoms from early childhood onward. Longitudinal analysis in the proband (IV26) revealed the exceptional combination of congenital offset and substantial early progression. Most of the threshold levels differed significantly between the frequencies within each age group and, at the high frequencies (2-8 kHz), between the two age groups covered by generations IV and III (ages 30-38 years and 58-74 years, respectively); the latter could be attributed to presbyacusis. Various caloric abnormalities, including areflexia, were found in about half (8/17) of the tested subjects with sensorineural hearing impairment.Conclusions: Correction for age, hearing impairment-presumably present and stationary from an early age onward-showed the worst or second-worst threshold usually at 1, 2, and 6 kHz (35-40 dB) or 8 kHz (50 dB), whereas the best or second-best threshold was found at 0.25 to 0.5 and 4 kHz (25 dB). Presbyacusis, presumably from the fourth decade of life onward, caused a change of the typically shaped audiogram described as midfrequency hearing impairment with additional high-frequency impairment.