PDF(Pubmed)
Abstract：
Individuals with Kabuki syndrome type 1 (KS1) often have hearing loss recognized in middle childhood. Current clinical dogma suggests that this phenotype is caused by frequent infections due to the immune deficiency in KS1 and/or secondary to structural abnormalities of the ear. To clarify some aspects of hearing loss, we collected information on hearing status from 21 individuals with KS1 and found that individuals have both sensorineural and conductive hearing loss, with the average age of presentation being 7 years. Our data suggest that while ear infections and structural abnormalities contribute to the observed hearing loss, these factors do not explain all loss. Using a KS1 mouse model, we found hearing abnormalities from hearing onset, as indicated by auditory brainstem response measurements. In contrast to mouse and human data for CHARGE syndrome, a disorder possessing overlapping clinical features with KS and a well-known cause of hearing loss and structural inner ear abnormalities, there are no apparent structural abnormalities of the cochlea in KS1 mice. The KS1 mice also display diminished distortion product otoacoustic emission levels, which suggests outer hair cell dysfunction. Combining these findings, our data suggests that KMT2D dysfunction causes sensorineural hearing loss compounded with external factors, such as infection.
摘要：
患有Kabuki综合征1型（KS1）的个体通常在儿童中期就有听力损失。目前的临床教条表明，这种表型是由于KS1中的免疫缺陷引起的频繁感染和/或继发于耳朵的结构异常。为了澄清听力损失的一些方面，我们收集了21名KS1患者的听力状态信息，发现这些人同时患有感音神经性和传导性听力损失，演示的平均年龄为7岁。我们的数据表明，虽然耳部感染和结构异常会导致观察到的听力损失，这些因素不能解释所有的损失。使用KS1小鼠模型，我们从听力开始就发现了听力异常，如听觉脑干反应测量所示。与CHARGE综合征的小鼠和人类数据相反，一种与KS具有重叠临床特征的疾病，并且是众所周知的听力损失和结构性内耳异常的原因，在KS1小鼠中没有明显的耳蜗结构异常。KS1小鼠还显示失真产物耳声发射水平降低，这表明外毛细胞功能障碍。结合这些发现，我们的数据表明，KMT2D功能障碍会导致感音神经性听力损失，并伴有外部因素，如感染。
