@article {615,
	title = {Mutation in the intracellular chloride channel CLCC1 associated with autosomal recessive retinitis pigmentosa.},
	journal = {PLoS Genet},
	volume = {14},
	year = {2018},
	month = {2018 08},
	pages = {e1007504},
	abstract = {<p>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.</p>},
	keywords = {Animals, Asian Continental Ancestry Group, Cell Line, Chloride Channels, Cytoplasm, Eye Proteins, HEK293 Cells, Homozygote, Humans, Mice, Mice, Knockout, Mutation, Missense, Pakistan, Retina, Retinal Cone Photoreceptor Cells, Retinal Rod Photoreceptor Cells, Retinitis Pigmentosa, Zebrafish},
	issn = {1553-7404},
	doi = {10.1371/journal.pgen.1007504},
	author = {Li, Lin and Jiao, Xiaodong and D{\textquoteright}Atri, Ilaria and Ono, Fumihito and Nelson, Ralph and Chan, Chi-Chao and Nakaya, Naoki and Ma, Zhiwei and Ma, Yan and Cai, Xiaoying and Zhang, Longhua and Lin, Siying and Hameed, Abdul and Chioza, Barry A and Hardy, Holly and Arno, Gavin and Hull, Sarah and Khan, Muhammad Imran and Fasham, James and Harlalka, Gaurav V and Michaelides, Michel and Moore, Anthony T and Coban Akdemir, Zeynep Hande and Jhangiani, Shalini and Lupski, James R and Cremers, Frans P M and Qamar, Raheel and Salman, Ahmed and Chilton, John and Self, Jay and Ayyagari, Radha and Kabir, Firoz and Naeem, Muhammad Asif and Ali, Muhammad and Akram, Javed and Sieving, Paul A and Riazuddin, Sheikh and Baple, Emma L and Riazuddin, S Amer and Crosby, Andrew H and Hejtmancik, J Fielding}
}
@article {157,
	title = {Mutation of ATF6 causes autosomal recessive achromatopsia.},
	journal = {Hum Genet},
	volume = {134},
	year = {2015},
	month = {2015 Sep},
	pages = {941-50},
	abstract = {<p>Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1-q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans. </p>},
	keywords = {Activating Transcription Factor 6, Adolescent, Animals, Asian Continental Ancestry Group, Color Vision Defects, Consanguinity, DNA Mutational Analysis, Exome, Female, Frameshift Mutation, Genotyping Techniques, Homozygote, Humans, Limit of Detection, Male, Mice, Mice, Inbred C57BL, Pakistan, Pedigree, Phenotype, Retina, Signal Transduction},
	issn = {1432-1203},
	doi = {10.1007/s00439-015-1571-4},
	author = {Ansar, Muhammad and Santos-Cortez, Regie Lyn P and Saqib, Muhammad Arif Nadeem and Zulfiqar, Fareeha and Lee, Kwanghyuk and Ashraf, Naeem Mahmood and Ullah, Ehsan and Wang, Xin and Sajid, Sundus and Khan, Falak Sher and Amin-ud-Din, Muhammad and Smith, Joshua D and Shendure, Jay and Bamshad, Michael J and Nickerson, Deborah A and Hameed, Abdul and Riazuddin, Saima and Ahmed, Zubair M and Ahmad, Wasim and Leal, Suzanne M}
}
