最近,，美國(guó)邁阿密大學(xué)米勒醫(yī)學(xué)院的研究人員發(fā)現(xiàn),，基因PRPS1對(duì)內(nèi)耳的發(fā)育至關(guān)重要，該基因發(fā)生突變將導(dǎo)致男性聽力喪失,。這項(xiàng)研究報(bào)告發(fā)表在12月7日American Journal of Human Genetics雜志上,。
研究發(fā)現(xiàn)，PRPS1基因與DFN2相關(guān),，DFN2是一種主要影響男性的漸進(jìn)性失聰，患DFN2的男性在5～15歲間開始逐漸喪失聽力,，而患病男性的母親若攜帶缺陷性PRPS1基因也會(huì)出現(xiàn)相同的聽力喪失的癥狀,，不過癥狀出現(xiàn)的時(shí)間一般較晚。
PRPS1基因編碼磷酸核糖焦磷酸合成酶1(phosphoribosylpyrophosphate synthetase 1),，該酶能夠生產(chǎn)并調(diào)控磷酸核糖焦磷酸,，在內(nèi)耳的發(fā)育過程中起關(guān)鍵作用。研究人員在PRPS1基因中發(fā)現(xiàn)了四個(gè)突變,，這些突變導(dǎo)致PRPS合成酶的表達(dá)水平顯著下降,，導(dǎo)致內(nèi)耳毛細(xì)胞發(fā)育缺陷，最終導(dǎo)致漸進(jìn)性失聰,。
了解到PRPP合成酶1基因的表達(dá)水平是導(dǎo)致失聰?shù)年P(guān)鍵原因,，課題組目前正在探究能否利用酶替代療法幫助患DFN2的男性恢復(fù)聽力。研究人員還認(rèn)為,，可以利用PRPP1作為DFN2一種遺傳標(biāo)記物,，來檢測(cè)剛出生的孩子是否會(huì)發(fā)生這種漸進(jìn)性失聰。（生物谷Bioon.com）
更多聽力研究：
Neuron：揭秘敏銳聽力原因
PNAS：噪音影響嬰幼兒聽力和智力發(fā)育
Nature Neuroscience：知覺訓(xùn)練可修復(fù)大腦聽力功能損傷
STEM CELLS：培育出內(nèi)耳毛細(xì)胞 有望恢復(fù)耳聾患者聽力
生物谷推薦原始出處：
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.
