Whole-Exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal- Recessive Complete Congenital Stationary Night Blindness Isabelle Audo, Kinga.

Slides:

Advertisements

Similar presentations

Previous Estimates of Mitochondrial DNA Mutation Level Variance Did Not Account for Sampling Error: Comparing the mtDNA Genetic Bottleneck in Mice and.

Advertisements

Volume 17, Issue 4, Pages (April 2009)

Invest. Ophthalmol. Vis. Sci ;54(9): doi: /iovs Figure Legend:

From: Efficient Gene Transfer into Retinal Cells Using Adenoviral Vectors: Dependence on Receptor Expression Invest. Ophthalmol. Vis. Sci ;45(6):

From: Deficiency of SHP-1 Protein-Tyrosine Phosphatase in “Viable Motheaten” Mice Results in Retinal Degeneration Invest. Ophthalmol. Vis. Sci ;47(3):

Protein-Truncation Mutations in the RP2 Gene in a North American Cohort of Families with X-Linked Retinitis Pigmentosa Alan J. Mears, Linn Gieser, Denise.

Pierre Mattar, Johan Ericson, Seth Blackshaw, Michel Cayouette Neuron

Whole-Exome Sequencing Identifies LRIT3 Mutations as a Cause of Autosomal- Recessive Complete Congenital Stationary Night Blindness Christina Zeitz, Samuel G.

Khanh-Nhat Tran-Viet, Caldwell Powell, Veluchamy A

Mutations in IMPG1 Cause Vitelliform Macular Dystrophies

Volume 26, Issue 2, Pages (May 2000)

Volume 37, Issue 5, Pages (March 2003)

Biallelic Mutations in the Autophagy Regulator DRAM2 Cause Retinal Dystrophy with Early Macular Involvement Mohammed E. El-Asrag, Panagiotis I. Sergouniotis,

TMEM126A, Encoding a Mitochondrial Protein, Is Mutated in Autosomal-Recessive Nonsyndromic Optic Atrophy Sylvain Hanein, Isabelle Perrault, Olivier Roche,

A Mutation in ZNF513, a Putative Regulator of Photoreceptor Development, Causes Autosomal-Recessive Retinitis Pigmentosa Lin Li, Naoki Nakaya, Venkata.

A Missense Mutation in PRPF6 Causes Impairment of pre-mRNA Splicing and Autosomal-Dominant Retinitis Pigmentosa Goranka Tanackovic, Adriana Ransijn,

Pias3-Dependent SUMOylation Directs Rod Photoreceptor Development

Volume 34, Issue 2, Pages (April 2002)

A Truncating Mutation of CEP135 Causes Primary Microcephaly and Disturbed Centrosomal Function Muhammad Sajid Hussain, Shahid Mahmood Baig, Sascha Neumann,

Heterozygous NTF4 Mutations Impairing Neurotrophin-4 Signaling in Patients with Primary Open-Angle Glaucoma Francesca Pasutto, Tomoya Matsumoto, Christian.

Mutations in TOPORS Cause Autosomal Dominant Retinitis Pigmentosa with Perivascular Retinal Pigment Epithelium Atrophy Christina F. Chakarova, Myrto.

Homozygosity Mapping Reveals Null Mutations in FAM161A as a Cause of Autosomal- Recessive Retinitis Pigmentosa Dikla Bandah-Rozenfeld, Liliana Mizrahi-Meissonnier,

A Nonsense Mutation in PDE6H Causes Autosomal-Recessive Incomplete Achromatopsia Susanne Kohl, Frauke Coppieters, Françoise Meire, Simone Schaich, Susanne.

Biallelic Mutations in GNB3 Cause a Unique Form of Autosomal-Recessive Congenital Stationary Night Blindness Ajoy Vincent, Isabelle Audo, Erika Tavares,

A Missense Mutation in DHDDS, Encoding Dehydrodolichyl Diphosphate Synthase, Is Associated with Autosomal-Recessive Retinitis Pigmentosa in Ashkenazi.

Immunosuppression via Loss of IL2rγ Enhances Long-Term Functional Integration of hESC-Derived Photoreceptors in the Mouse Retina Jie Zhu, Helen Cifuentes,

Mutations in TRPM1 Are a Common Cause of Complete Congenital Stationary Night Blindness Maria M. van Genderen, Mieke M.C. Bijveld, Yvonne B. Claassen,

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

A Mutation in ZNF513, a Putative Regulator of Photoreceptor Development, Causes Autosomal-Recessive Retinitis Pigmentosa Lin Li, Naoki Nakaya, Venkata.

Volume 31, Issue 6, Pages (September 2001)

Volume 5, Issue 6, Pages (June 2004)

S. Amer Riazuddin, Amber Shahzadi, Christina Zeitz, Zubair M

Volume 15, Issue 6, Pages (March 2005)

Mutations in CABP4, the Gene Encoding the Ca2+-Binding Protein 4, Cause Autosomal Recessive Night Blindness Christina Zeitz, Barbara Kloeckener-Gruissem,

Msx1-Positive Progenitors in the Retinal Ciliary Margin Give Rise to Both Neural and Non-neural Progenies in Mammals Marie-Claude Bélanger, Benoit Robert,

The retinal pigmented epithelium is required for development and maintenance of the mouse neural retina Sophie M. Raymond, Ian J. Jackson Current Biology

Volume 4, Issue 5, Pages (November 2001)

Mutation of Solute Carrier SLC16A12 Associates with a Syndrome Combining Juvenile Cataract with Microcornea and Renal Glucosuria Barbara Kloeckener-Gruissem,

Alpha-B Crystallin Gene (CRYAB) Mutation Causes Dominant Congenital Posterior Polar Cataract in Humans Vanita Berry, Peter Francis, M. Ashwin Reddy,

Volume 3, Issue 4, Pages (April 2001)

Volume 30, Issue 1, Pages (July 2014)

Spatially and Temporally Regulated NRF2 Gene Therapy Using Mcp-1 Promoter in Retinal Ganglion Cell Injury Kosuke Fujita, Koji M. Nishiguchi, Yukihiro.

Volume 81, Issue 4, Pages (February 2014)

Debra E. Bramblett, Mark E. Pennesi, Samuel M. Wu, Ming-Jer Tsai

Volume 43, Issue 6, Pages (September 2004)

Volume 17, Issue 5, Pages (May 2009)

Isabelle Audo, Susanne Kohl, Bart P. Leroy, Francis L

Volume 131, Issue 2, Pages (October 2007)

J. Fielding Hejtmancik, Xiaodong Jiao, Anren Li, Yuri V

Mutations in SPATA7 Cause Leber Congenital Amaurosis and Juvenile Retinitis Pigmentosa Hui Wang, Anneke I. den Hollander, Yalda Moayedi, Abuduaini Abulimiti,

Molecular Therapy - Methods & Clinical Development

Absence of a retinal phenotype in CIB2−/− mice

Autosomal-Dominant Striatal Degeneration Is Caused by a Mutation in the Phosphodiesterase 8B Gene Silke Appenzeller, Anja Schirmacher, Hartmut Halfter,

Volume 37, Issue 5, Pages (March 2003)

A Missense Mutation in DHDDS, Encoding Dehydrodolichyl Diphosphate Synthase, Is Associated with Autosomal-Recessive Retinitis Pigmentosa in Ashkenazi.

Regeneration: New Neurons Wire Up

Figure 1 A B GCL NBL ED18.5 PND3 PND6 GCL

Dror Sharon, Michael A. Sandberg, Vivian W

Inhomogeneous Encoding of the Visual Field in the Mouse Retina

Mutations in CNNM4 Cause Recessive Cone-Rod Dystrophy with Amelogenesis Imperfecta Bozena Polok, Pascal Escher, Aude Ambresin, Eliane Chouery, Sylvain.

Identification and Functional Consequences of a New Mutation (E155G) in the Gene for GCAP1 That Causes Autosomal Dominant Cone Dystrophy Susan E. Wilkie,

Mutations in the Human Orthologue of the Mouse underwhite Gene (uw) Underlie a New Form of Oculocutaneous Albinism, OCA4 J.M. Newton, Orit Cohen-Barak,

Volume 9, Issue 2, Pages (February 2004)

Volume 27, Issue 11, Pages e3 (June 2019)

Mutation of CERKL, a Novel Human Ceramide Kinase Gene, Causes Autosomal Recessive Retinitis Pigmentosa (RP26) Miquel Tuson, Gemma Marfany, Roser Gonzàlez-Duarte

Fig. 8. Electron micrographs taken from 8-week glaucoma retina

Mark W. Hankins, Steven Hughes Current Biology

A Truncating Mutation of TRAPPC9 Is Associated with Autosomal-Recessive Intellectual Disability and Postnatal Microcephaly Ganeshwaran H. Mochida, Muhammad.

The predicted new isoform of PCP2 is expressed in retinal ON bipolar cells. The predicted new isoform of PCP2 is expressed in retinal ON bipolar cells.

Volume 131, Issue 2, Pages (October 2007)

Presentation transcript:

Whole-Exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal- Recessive Complete Congenital Stationary Night Blindness Isabelle Audo, Kinga Bujakowska, Elise Orhan, Charlotte M. Poloschek, Sabine Defoort-Dhellemmes, Isabelle Drumare, Susanne Kohl, Tien D. Luu, Odile Lecompte, Eberhart Zrenner, Marie-Elise Lancelot, Aline Antonio, Aurore Germain, Christelle Michiels, Claire Audier, Mélanie Letexier, Jean-Paul Saraiva, Bart P. Leroy, Francis L. Munier, Saddek Mohand-Saïd, Birgit Lorenz, Christoph Friedburg, Markus Preising, Ulrich Kellner, Agnes B. Renner, Veselina Moskova-Doumanova, Wolfgang Berger, Bernd Wissinger, Christian P. Hamel, Daniel F. Schorderet, Elfride De Baere, Dror Sharon, Eyal Banin, Samuel G. Jacobson, Dominique Bonneau, Xavier Zanlonghi, Guylene Le Meur, Ingele Casteels, Robert Koenekoop, Vernon W. Long, Francoise Meire, Katrina Prescott, Thomy de Ravel, Ian Simmons, Hoan Nguyen, Hélène Dollfus, Olivier Poch, Thierry Léveillard, Kim Nguyen-Ba-Charvet, José-Alain Sahel, Shomi S. Bhattacharya, Christina Zeitz The American Journal of Human Genetics Volume 90, Issue 2, Pages 321-330 (February 2012) DOI: 10.1016/j.ajhg.2011.12.007 Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 1 GPR179 mutations in CSNB. (A) GPR179 structure containing 11 coding exons (NM_001004334.2). Different mutations identified in cCSNB patients are depicted. (B) The specific domains for GPR179 were estimated by a prediction program (UniProtKB/Swiss-Prot). The American Journal of Human Genetics 2012 90, 321-330DOI: (10.1016/j.ajhg.2011.12.007) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 2 3D Model of the Transmembrane Region of GPR179 (A) 3D homology model based on the 3D model of the wild-type squid rhodopsin (2ZIY). Wild-type Gly455 and His603 residues are indicated in green and the mutated Asp455 and Tyr603 in orange. (B) Superimposition of 3D models of the wild-type residues and the Gly455Asp alteration (aspartate in orange). The American Journal of Human Genetics 2012 90, 321-330DOI: (10.1016/j.ajhg.2011.12.007) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 3 Indirect Expression Analysis of Gpr179 in rd1 and Wild-Type Mice Expression of Gpr179 (1459268_at) compared to the expression of Nyx (1446344_at, a known molecule expressed in the inner nuclear layer, also implicated in cCSNB) during rod degeneration in the rd1 mouse. Neural retinas from rd1 and wild-type mice on identical genetic backgrounds47 were hybridized to the mouse genome 430 2.0 array (Affymetrix, High Wycombe, UK). The expression profiles are similar from postnatal day (PND) 5 to PND12. Thereafter, the expression of Gpr179, as well as Nyx, increases in the rd1 retina. This phenomenon correlates temporally with the loss of rod photoreceptor cells and is likely due to the unaffected inner retinal cells in the rd1 specimen at this age. The American Journal of Human Genetics 2012 90, 321-330DOI: (10.1016/j.ajhg.2011.12.007) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 4 Gpr179 Immunohistochemistry on Retinal Sections of Wild-Type Mice GPR179 signal (green) in the OPL and ILM double labeled with other retinal markers (red) were detected in wild-type mice by confocal microscopy. The scale bar represents 20 μm. The following abbreviations are used: ONL, outer nuclear layer; OPL, outer plexiform layer; INL, inner nuclear layer; GCL, ganglion cell layer; and ILM, inner limiting membrane. Gpr179 did not colocalize with the presynaptic marker Basoon (A), the ON-bipolar cell markers Goα (B) and PKCα (C), or with the ganglion cell labeled with calretinin (D). Some cells in the upper part of INL were surrounded by specific Gpr179 staining (arrow in A). The shape and the localization might indicate that these cells represent horizontal cells. Bipolar cell dendrites, stained with PKCα seem to surround Gpr179 (arrow in C). Calretinin antibody labeled specifically the ganglion cells, and their dendrites did not colocalize with Gpr179 (arrow in D). Instead, it seems that Gpr179 is highly concentrated in Müller cell endfeet (D); similar results have been previously shown for a potassium channel Kir4.1.31 The American Journal of Human Genetics 2012 90, 321-330DOI: (10.1016/j.ajhg.2011.12.007) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 5 Genes Underlying CSNB Different forms of CSNB in human are classified according to their electroretinographic feature, mode of inheritance, clinical phenotype, and mutated genes. Patients discussed herein show a complete Schubert-Bornschein type of ERG. The following abbreviations are used: cCSNB, complete CSNB; icCSNB, incomplete CSNB; ar, autosomal recessive; ad, autosomal dominant. Genes are indicated in italics and underlined. Chromosomal location is given between brackets. The phenotype of patients with mutations in icCSNB is more variable and can even lead to progressive cone or cone-rod dystrophy.1 The American Journal of Human Genetics 2012 90, 321-330DOI: (10.1016/j.ajhg.2011.12.007) Copyright © 2012 The American Society of Human Genetics Terms and Conditions