Kemperman Martijn H, De Leenheer Els M R, Huygen Patrick L M, van Wijk Erwin, van Duijnhoven Gerard, Cremers Frans P M, Kremer Hannie, Cremers Cor W R J
Department of Otorhinolaryngology, University Medical Center Nijmegen, Nijmegen, The Netherlands.
Arch Otolaryngol Head Neck Surg. 2004 Mar;130(3):281-8. doi: 10.1001/archotol.130.3.281.
To perform linkage analysis and to outline hearing loss characteristics in a family exhibiting a nonsyndromic, autosomal dominant type of progressive sensorineural hearing loss.
Genetic analysis was performed using microsatellite markers. Audiometric data were collected and analyzed longitudinally. Sigmoidal dose-response curves enabled us to perform nonlinear regression analysis per frequency and on phoneme recognition scores. Speech recognition scores were compared with those of DFNA2, DFNA5, DFNA9, and presbyacusis subjects.
Affected family members of a Dutch family (W99-060).
We revealed linkage of hearing loss to the DFNA20/26 locus (maximum logarithm of odds score, 3.1 at theta=0.04) and reduced the critical region from 12 to 9.5 centimorgans. Patients younger than 15 years already showed gently downsloping audiograms. At ages 15 to 20 and 25 to 40 years, hearing loss was profound at 8 kHz and 1 to 4 kHz, respectively. The 0.25- to 0.5-kHz thresholds showed more gradual progression by about 1.5 to 2 dB/y. From about age 40 years onward, hearing was residual. Hearing impairment took a more severe course than in a known DFNA20 family. Score recognition in DFNA20/26 subjects was better than in DFNA9 subjects at any pure-tone average (1-4 kHz) threshold. Compared with subjects having DFNA2 and DFNA5, speech recognition in those with DFNA20/26 scored better at threshold levels below 85 dB hearing level, but worse at levels above 90 dB. Compared with presbyacusis subjects, those with DFNA20/26 scored better in speech recognition at levels below 100 dB and worse at levels above 100 dB.
Autosomal dominant hearing loss is linked to the DFNA20/26 locus in this Dutch family. The critical region is reduced from 12 to 9.5 centimorgans. Phenotypically, patients are more severely affected than those of a known DFNA20 family.
对一个表现为非综合征性常染色体显性进行性感音神经性听力损失的家系进行连锁分析，并概述其听力损失特征。
使用微卫星标记进行基因分析。纵向收集并分析听力测定数据。S形剂量反应曲线使我们能够按频率和音素识别分数进行非线性回归分析。将言语识别分数与DFNA2、DFNA5、DFNA9和老年性耳聋受试者的分数进行比较。
一个荷兰家系（W99 - 060）的受累家庭成员。
我们发现听力损失与DFNA20/26位点连锁（最大优势对数分数，在θ = 0.04时为3.1），并将关键区域从12厘摩缩小至9.5厘摩。15岁以下的患者已经表现出轻度下降型听力图。在15至20岁以及25至40岁时，听力损失分别在8千赫和1至4千赫时严重。0.25至0.5千赫的阈值以每年约1.5至2分贝的速度更缓慢地进展。从大约40岁起，听力仅存残余。听力损害的病程比已知的DFNA20家系中的患者更严重。在任何纯音平均（1 - 4千赫）阈值下，DFNA20/26受试者的分数识别都优于DFNA9受试者。与患有DFNA2和DFNA5的受试者相比，DFNA20/26受试者在听力水平低于85分贝的阈值水平时言语识别得分更好，但在高于90分贝的水平时更差。与老年性耳聋受试者相比，DFNA20/26受试者在低于100分贝的水平时言语识别得分更好，而在高于100分贝的水平时更差。
在这个荷兰家系中，常染色体显性听力损失与DFNA20/26位点连锁。关键区域从12厘摩缩小至9.5厘摩。从表型上看，患者比已知的DFNA20家系中的患者受影响更严重。
