Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration
Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration
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DOI：
10.1093/brain/aws317
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发表时间：
2013-01-01
期刊：
影响因子：
14.5
通讯作者：
Brewer, Carmen C.
中科院分区：
文献类型：
--
作者：
Totonchy, Mariam B.;Tamura, Deborah;Brewer, Carmen C.
为了评估DNA修复在维持听力功能和神经完整性中的作用，我们检查了1971年至2012年在美国国立卫生研究院检查的所有至少有一个完整听力图的着色性干皮病患者的听力状况、神经功能、DNA修复互补组和在最小日晒下急性烧伤史。79例患者，年龄1-61岁，诊断为色素性干皮病（n = 77）或色素性干皮病/Cockayne综合征（n = 2）。共包括178个听力图。79例患者中有23例（29%）出现临床显著性听力损失（bbb20 dB）。在17例色素性干皮病型神经退行性变患者中，13例（76%）出现听力损失，所有17例患者均为补体组A型或D型色素性干皮病，并报告在少量阳光照射下急性烧伤。18%的患者（10/55）在最小的阳光照射下出现急性烧伤，而没有着色性干皮病型神经变性。重度色素性干皮病神经退行性变患者颞骨组织学显示耳蜗感觉上皮及神经元明显萎缩。色素性干皮病合并色素性干皮病型神经退行性变患者发现临床显著性听力损失的平均年龄为19岁，比国际标准预测的年龄年轻54岁。4个频率（0.5/1/2/4 kHz）纯音平均值与神经退行性变程度相关（P < 0.001）。在4-30岁的着色性干皮病患者中，四频纯音平均epsilon 10 dB听力损失与发生着色性干皮病型神经变性的风险增加39倍（P = 0.002）相关。听力损失的严重程度与色素性干皮病型神经退行性变患者的神经功能下降平行。听力测量结果、补体组、日晒后急性烧伤和年龄是色素性干皮病型神经变性的重要预测因素。这些结果证明DNA修复对于维持听觉系统的神经完整性至关重要。
To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1-61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included. Clinically significant hearing loss (> 20 dB) was present in 23 (29%) of 79 patients. Of the 17 patients with xeroderma pigmentosum-type neurological degeneration, 13 (76%) developed hearing loss, and all 17 were in complementation groups xeroderma pigmentosum type A or type D and reported acute burning on minimal sun exposure. Acute burning on minimal sun exposure without xeroderma pigmentosum-type neurological degeneration was present in 18% of the patients (10/55). Temporal bone histology in a patient with severe xeroderma pigmentosum-type neurological degeneration revealed marked atrophy of the cochlear sensory epithelium and neurons. The 19-year mean age of detection of clinically significant hearing loss in the patients with xeroderma pigmentosum with xeroderma pigmentosum-type neurological degeneration was 54 years younger than that predicted by international norms. The four frequency (0.5/1/2/4 kHz) pure-tone average correlated with degree of neurodegeneration (P < 0.001). In patients with xeroderma pigmentosum, aged 4-30 years, a four-frequency pure-tone average epsilon 10 dB hearing loss was associated with a 39-fold increased risk (P = 0.002) of having xeroderma pigmentosum-type neurological degeneration. Severity of hearing loss parallels neurological decline in patients with xeroderma pigmentosum-type neurological degeneration. Audiometric findings, complementation group, acute burning on minimal sun exposure and age were important predictors of xeroderma pigmentosum-type neurological degeneration. These results provide evidence that DNA repair is critical in maintaining neurological integrity of the auditory system.