最近,美国迈阿密大学米勒医学院的研究人员发现,基因PRPS1对内耳的发育至关重要,该基因发生突变将导致男性听力丧失。这项研究报告发表在12月7日American Journal of Human Genetics杂志上。
研究发现,PRPS1基因与DFN2相关,DFN2是一种主要影响男性的渐进性失聪,患DFN2的男性在5~15岁间开始逐渐丧失听力,而患病男性的母亲若携带缺陷性PRPS1基因也会出现相同的听力丧失的症状,不过症状出现的时间一般较晚。
PRPS1基因编码磷酸核糖焦磷酸合成酶1(phosphoribosylpyrophosphate synthetase 1),该酶能够生产并调控磷酸核糖焦磷酸,在内耳的发育过程中起关键作用。研究人员在PRPS1基因中发现了四个突变,这些突变导致PRPS合成酶的表达水平显著下降,导致内耳毛细胞发育缺陷,最终导致渐进性失聪。
了解到PRPP合成酶1基因的表达水平是导致失聪的关键原因,课题组目前正在探究能否利用酶替代疗法帮助患DFN2的男性恢复听力。研究人员还认为,可以利用PRPP1作为DFN2一种遗传标记物,来检测刚出生的孩子是否会发生这种渐进性失聪。(生物谷Bioon.com)
更多听力研究:
Neuron:揭秘敏锐听力原因
PNAS:噪音影响婴幼儿听力和智力发育
Nature Neuroscience:知觉训练可修复大脑听力功能损伤
STEM CELLS:培育出内耳毛细胞 有望恢复耳聋患者听力
生物谷推荐原始出处:
The American Journal of Human Genetics, 17 December 2009
Loss-of-Function Mutations in the PRPS1 Gene Cause a Type of Nonsyndromic X-linked Sensorineural Deafness, DFN2
Xuezhong Liu1, 2, 11, Dongyi Han2, 11, Jianzhong Li2, Bing Han2, Xiaomei Ouyang1, Jing Cheng2, Xu Li3, 4, Zhanguo Jin2, Youqin Wang5, Maria Bitner-Glindzicz6, Xiangyin Kong7, Heng Xu7, Albena Kantardzhieva8, Roland D. Eavey8, Christine E. Seidman9, 10, Jonathan G. Seidman9, 10, Li L. Du1, Zheng-Yi Chen8, Pu Dai2, Maikun Teng3, 4, Denise Yan1 and Huijun Yuan2, ,
1 Department of Otolaryngology, University of Miami, Miami, FL 33136, USA
2 Institute Of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, China
3 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230026, China
4 Key Laboratory of Structural Biology, Chinese Academy of Sciences, Hefei 230026, China
5 Hearing Center, Guizhou Provincial People's Hospital, GuiYang 550002, China
6 Clinical and Molecular Genetics, UCL Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK
7 Health Science Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Second Medical University, 225 South Chong Qing Road, Shanghai 200025, China
8 Eaton-Peabody Laboratory, Department of Otolaryngology, The Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston 02114, USA
9 Harvard Medical School, Department of Genetics, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
10 Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
We report a large Chinese family with X-linked postlingual nonsyndromic hearing impairment in which the critical linkage interval spans a genetic distance of 5.41 cM and a physical distance of 15.1 Mb that overlaps the DFN2 locus. Mutation screening of the PRPS1 gene in this family and in the three previously reported DFN2 families identified four different missense mutations in PRPS1. These mutations result in a loss of phosphoribosyl pyrophosphate (PRPP) synthetase 1 activity, as was shown in silico by structural analysis and was shown in vitro by enzymatic activity assays in erythrocytes and fibroblasts from patients. By in situ hybridization, we demonstrate expression of Prps1 in murine vestibular and cochlea hair cells, with continuous expression in hair cells and postnatal expression in the spiral ganglion. Being the second identified gene associated with X-linked nonsyndromic deafness, PRPS1 will be a good candidate gene for genetic testing for X-linked nonsyndromic hearing loss.