Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Hear Res. 2011 Dec;282(1-2):167-77. doi: 10.1016/j.heares.2011.08.010. Epub 2011 Aug 27.
Investigation of the audiometric characteristics of a large Dutch DFNX4 family with a p.Glu72X mutation in the SMPX gene.
Sixty family members participated in this study and examination consisted of medical history, otoscopy, pure tone and speech audiometry. Linkage and mutation analysis revealed a pathogenic mutation in the SMPX gene.
All 25 mutation carriers exhibited hearing impairment, except one woman aged 25 years. The men (n = 10) showed more severe hearing impairment than the women (n = 14) and already at a younger age. The age of onset according to history was 2-10 years (mean: 3.3 years) in men and 3-48 years (mean: 26.4 years) in women. In the men, severe threshold deterioration mainly occurred during the first two decades of life, especially at the higher frequencies. The women showed milder threshold deterioration and more pronounced across-subjects and individual inter-aural variation, especially at 2-8 kHz. Longitudinal linear regression analysis demonstrated significant progression of at least two frequencies in five individuals (3 men and 2 women). The speech recognition scores of the mutation carriers with hearing impairment were decreased at relatively young ages compared to a reference group of patients with only presbycusis, especially in men. However, all these patients tended to have better speech recognition scores than the presbycusis patients at matching PTA(1,2,4 kHz) levels.
This study demonstrates the phenotypic heterogeneity in this large family with an X-linked pattern of inherited sensorineural hearing impairment. The men showed more severe hearing impairment at a younger age with more pronounced progression during the first two decades of life, while women demonstrated less severe hearing impairment with more gradual progression and a wider variation in age of onset, degree of hearing impairment and inter-aural asymmetry in thresholds.
研究一个大型荷兰 DFNX4 家系的听力特征，该家系携带 SMPX 基因的 p.Glu72X 突变。
60 名家庭成员参与了这项研究，检查包括病史、耳镜检查、纯音和言语测听。连锁和突变分析显示 SMPX 基因存在致病性突变。
除了一名 25 岁的女性外，所有 25 名突变携带者均存在听力障碍。男性（n=10）的听力障碍比女性（n=14）更严重，发病年龄也更小。根据病史，男性的发病年龄为 2-10 岁（平均 3.3 岁），女性为 3-48 岁（平均 26.4 岁）。在男性中，严重的阈值恶化主要发生在生命的头二十年，尤其是在较高频率。女性的阈值恶化程度较轻，个体间和个体内的听力差异更为明显，尤其是在 2-8kHz。纵向线性回归分析显示，5 名个体（3 名男性和 2 名女性）至少有两个频率的听力呈进行性下降。听力受损的突变携带者的言语识别得分在相对年轻的年龄就比只有老年性聋的参考组患者下降，尤其是男性。然而，所有这些患者在匹配 PTA（1、2、4kHz）水平时，言语识别得分都比老年性聋患者好。
这项研究表明，在一个具有 X 连锁遗传性感觉神经性听力损失模式的大型家系中，存在表型异质性。男性在更年轻时出现更严重的听力损失，在生命的头二十年中听力下降更为明显，而女性则表现出较轻的听力损失，听力下降更缓慢，发病年龄、听力损失程度和阈值的个体间和个体内的不对称性变化更大。
