Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa

被引：28

作者：

Li, Lin ^{[1
,2
]}

Jiao, Xiaodong ^{[2
]}

D'Atri, Ilaria ^{[3
]}

Ono, Fumihito ^{[4
,5
]}

Nelson, Ralph ^{[6
]}

Chan, Chi-Chao ^{[7
]}

Nakaya, Naoki ^{[8
]}

Ma, Zhiwei ^{[2
]}

Ma, Yan ^{[2
]}

Cai, Xiaoying ^{[9
]}

Zhang, Longhua ^{[9
]}

Lin, Siying ^{[3
]}

Hameed, Abdul ^{[3
,10
]}

Chioza, Barry A. ^{[3
]}

Hardy, Holly ^{[3
]}

Arno, Gavin ^{[11
,12
]}

Hull, Sarah ^{[11
,12
]}

Khan, Muhammad Imran ^{[13
]}

Fasham, James ^{[3
,14
]}

Harlalka, Gaurav V. ^{[3
]}

Michaelides, Michel ^{[11
,12
]}

Moore, Anthony T. ^{[11
,12
,15
]}

Akdemir, Zeynep Hande Coban ^{[16
]}

Jhangiani, Shalini ^{[17
]}

Lupski, James R. ^{[16
,17
,18
,19
]}

Cremers, Frans P. M. ^{[20
]}

Qamar, Raheel ^{[13
]}

Salman, Ahmed ^{[21
]}

Chilton, John ^{[3
]}

Self, Jay ^{[21
]}

Ayyagari, Radha ^{[22
]}

Kabir, Firoz ^{[23
,24
]}

Naeem, Muhammad Asif ^{[23
]}

Ali, Muhammad ^{[23
,24
]}

Akram, Javed ^{[25
,26
]}

Sieving, Paul A. ^{[27
]}

Riazuddin, Sheikh ^{[23
,24
,25
]}

Baple, Emma L. ^{[3
,14
]}

Riazuddin, S. Amer ^{[23
,24
]}

Crosby, Andrew H. ^{[3
]}

Hejtmancik, J. Fielding ^{[2
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Ophthalmol, Shanghai, Peoples R China

[2] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA

[3] Royal Devon & Exeter NHS Fdn, RILD Wellcome Wolfson Ctr, Exeter, Devon, England

[4] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Bethesda, MD USA

[5] Osaka Med Coll, Dept Physiol, Takatsuki, Osaka, Japan

[6] NINDS, Unit Neural Circuits, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[7] NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA

[8] NEI, Sect Mol Mech Glaucoma, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA

[9] Univ Sci & Technol China, Sch Life Sci, Hefei, Anhui, Peoples R China

[10] IBGE, Islamabad, Pakistan

[11] UCL, Inst Ophthalmol, London, England

[12] Moorfields Eye Hosp, Dept Biosci, London, England

[13] COMSATS Inst Informat Technol, Fac Sci, Islamabad, Pakistan

[14] Royal Devon & Exeter NHS Fdn Trust, Dept Clin Genet, Exeter, Devon, England

[15] UCSF, Sch Med, Ophthalmol Dept, San Francisco, CA USA

[16] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA

[17] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[18] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[19] Texas Childrens Hosp, Houston, TX 77030 USA

[20] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[21] Univ Southampton, Fac Med, Southampton, Hants, England

[22] Univ Calif San Diego, Shiley Eye Inst, La Jolla, CA 92093 USA

[23] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan

[24] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA

[25] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan

[26] Shaheed Zulfiqar Ali Bhutto Med Univ, Natl Ctr Genet Dis, Islamabad, Pakistan

[27] NEI, NIH, Bethesda, MD 20892 USA

来源：

PLOS GENETICS | 2018年 / 14卷 / 08期

基金：

英国医学研究理事会; 中国国家自然科学基金;

关键词：

ISOLATED FROG RETINA; ENDOPLASMIC-RETICULUM; ER STRESS; GENE; DYSTROPHIES; EXPRESSION; DNA;

D O I：

10.1371/journal.pgen.1007504

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We identified a homozygous missense alteration (c. 75C> A, p. D25E) in CLCC1, encoding a presumptive intracellular chloride channel highly expressed in the retina, associated with autosomal recessive retinitis pigmentosa (arRP) in eight consanguineous families of Pakistani descent. The p. D25E alteration decreased CLCC1 channel function accompanied by accumulation of mutant protein in granules within the ER lumen, while siRNA knockdown of CLCC1 mRNA induced apoptosis in cultured ARPE- 19 cells. TALEN KO in zebrafish was lethal 11 days post fertilization. The depressed electroretinogram (ERG) cone response and cone spectral sensitivity of 5 dpf KO zebrafish and reduced eye size, retinal thickness, and expression of rod and cone opsins could be rescued by injection of wild type CLCC1 mRNA. Clcc1(+/-) KO mice showed decreased ERGs and photoreceptor number. Together these results strongly suggest that intracellular chloride transport by CLCC1 is a critical process in maintaining retinal integrity, and CLCC1 is crucial for survival and function of retinal cells.

引用

页数：29

共 44 条

[1] A method and server for predicting damaging missense mutations [J].

Adzhubei, Ivan A. ;

Schmidt, Steffen ;

Peshkin, Leonid ;

Ramensky, Vasily E. ;

Gerasimova, Anna ;

Bork, Peer ;

Kondrashov, Alexey S. ;

Sunyaev, Shamil R. .

NATURE METHODS, 2010, 7 (04) :248-249

[2] A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy [J].

Allikmets, R ;

Singh, N ;

Sun, H ;

Shroyer, NE ;

Hutchinson, A ;

Chidambaram, A ;

Gerrard, B ;

Baird, L ;

Stauffer, D ;

Peiffer, A ;

Rattner, A ;

Smallwood, P ;

Li, YX ;

Anderson, KL ;

Lewis, RA ;

Nathans, J ;

Leppert, M ;

Dean, M ;

Lupski, JR .

NATURE GENETICS, 1997, 15 (03) :236-246

[3] Lack of Interphotoreceptor Retinoid Binding Protein Caused by Homozygous Mutation of RBP3 Is Associated With High Myopia and Retinal Dystrophy [J].

Arno, Gavin ;

Hull, Sarah ;

Robson, Anthony G. ;

Holder, Graham E. ;

Cheetham, Michael E. ;

Webster, Andrew R. ;

Plagnol, Vincent ;

Moore, Anthony T. .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2015, 56 (04) :2358-2365

[4] In vivo genome editing using a high-efficiency TALEN system [J].

Bedell, Victoria M. ;

Wang, Ying ;

Campbell, Jarryd M. ;

Poshusta, Tanya L. ;

Starker, Colby G. ;

Krug, Randall G., II ;

Tan, Wenfang ;

Penheiter, Sumedha G. ;

Ma, Alvin C. ;

Leung, Anskar Y. H. ;

Fahrenkrug, Scott C. ;

Carlson, Daniel F. ;

Voytas, Daniel F. ;

Clark, Karl J. ;

Essner, Jeffrey J. ;

Ekker, Stephen C. .

NATURE, 2012, 491 (7422) :114-U133

[5] RISK-FACTORS FOR GENETIC TYPING AND DETECTION IN RETINITIS PIGMENTOSA [J].

BERSON, EL ;

ROSNER, B ;

SIMONOFF, E .

AMERICAN JOURNAL OF OPHTHALMOLOGY, 1980, 89 (06) :763-775

[6] RETINAL PHOTORECEPTOR DYSTROPHIES LL-EDWARD-JACKSON-MEMORIAL-LECTURE [J].

BIRD, AC .

AMERICAN JOURNAL OF OPHTHALMOLOGY, 1995, 119 (05) :543-562

[7] Relative Frequencies of Inherited Retinal Dystrophies and Optic Neuropathies in Southern France: Assessment of 21-year Data Management [J].

Bocquet, Beatrice ;

Lacroux, Annie ;

Surget, Marie-Odile ;

Baudoin, Corinne ;

Marquette, Virginie ;

Manes, Gael ;

Hebrard, Maxime ;

Senechal, Audrey ;

Delettre, Cecile ;

Roux, Anne-Francoise ;

Claustres, Mireille ;

Dhaenens, Claire-Marie ;

Rozet, Jean-Michel ;

Perrault, Isabelle ;

Bonnefont, Jean-Paul ;

Kaplan, Josseline ;

Dollfus, Helene ;

Amati-Bonneau, Patrizia ;

Bonneau, Dominique ;

Reynier, Pascal ;

Audo, Isabelle ;

Zeitz, Christina ;

Sahel, Jose Alain ;

Paquis-Flucklinger, Veronique ;

Calvas, Patrick ;

Arveiler, Benoit ;

Kohl, Suzanne ;

Wissinger, Bernd ;

Blanchet, Catherine ;

Meunier, Isabelle ;

Hamel, Christian P. .

OPHTHALMIC EPIDEMIOLOGY, 2013, 20 (01) :13-25

[8] Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa [J].

Chakarova, CF ;

Hims, MM ;

Bolz, H ;

Abu-Safieh, L ;

Patel, RJ ;

Papaioannou, MG ;

Inglehearn, CF ;

Keen, TJ ;

Willis, C ;

Moore, AT ;

Rosenberg, T ;

Webster, AR ;

Bird, AC ;

Gal, A ;

Hunt, D ;

Vithana, EN ;

Bhattacharya, SS .

HUMAN MOLECULAR GENETICS, 2002, 11 (01) :87-92

[9]

Chan CC, 1999, ARCH OPHTHALMOL-CHIC, V117, P625

[10] PRPF4 mutations cause autosomal dominant retinitis pigmentosa [J].

Chen, Xue ;

Liu, Yuan ;

Sheng, Xunlun ;

Tam, Pancy O. S. ;

Zhao, Kanxing ;

Chen, Xuejuan ;

Rong, Weining ;

Liu, Yani ;

Liu, Xiaoxing ;

Pan, Xinyuan ;

Chen, Li Jia ;

Zhao, Qingshun ;

Vollrath, Douglas ;

Pang, Chi Pui ;

Zhao, Chen .

HUMAN MOLECULAR GENETICS, 2014, 23 (11) :2926-2939

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