ABCB6 Mutations Cause Ocular Coloboma

Slides:

Advertisements

Similar presentations

Up-regulation of TGF-β1 mRNA expression in peripheral blood mononuclear cells of patients with chronic fatigue syndrome Hai-Ying Zhang, Zhan-Dong Liu,

Advertisements

Analysis of Pseudoxanthoma Elasticum–Causing Missense Mutants of ABCC6 In Vivo; Pharmacological Correction of the Mislocalized Proteins Viola Pomozi,

Multiple Synostoses Syndrome Is Due to a Missense Mutation in Exon 2 of FGF9 Gene Xiao-lin Wu, Ming-min Gu, Lei Huang, Xue-song Liu, Hong-xin Zhang, Xiao-yi.

A blood flow–dependent klf2a-NO signaling cascade is required for stabilization of hematopoietic stem cell programming in zebrafish embryos by Lu Wang,

Feng Liu, Maggie Walmsley, Adam Rodaway, Roger Patient Current Biology

Genetic Heterogeneity of Pseudoxanthoma Elasticum: The Chinese Signature Profile of ABCC6 and ENPP1 Mutations Liang Jin, Qiujie Jiang, Zhengsheng Wu,

Darryl Y. Nishimura, Lisa M. Baye, Rahat Perveen, Charles C

Arnd Heuser, Eva R. Plovie, Patrick T. Ellinor, Katja S

Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness Sedigheh.

Mutation Spectrum of the Survival of Motor Neuron 1 and Functional Analysis of Variants in Chinese Spinal Muscular Atrophy Yu-jin Qu, Jin-li Bai, Yan-yan.

James A. Poulter, Musallam Al-Araimi, Ivan Conte, Maria M

by Alex Bukrinsky, Kevin J. P

Stephan Züchner, Gaofeng Wang, Khanh-Nhat Tran-Viet, Martha A

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

Mutations in SLC33A1 Cause a Lethal Autosomal-Recessive Disorder with Congenital Cataracts, Hearing Loss, and Low Serum Copper and Ceruloplasmin Peter.

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

Eija Siintola, Meral Topcu, Nina Aula, Hannes Lohi, Berge A

Zebrafish as a Model System to Study Skin Biology and Pathology

Exome Sequencing and Functional Validation in Zebrafish Identify GTDC2 Mutations as a Cause of Walker-Warburg Syndrome M. Chiara Manzini, Dimira E. Tambunan,

Volume 10, Issue 2, Pages (August 2009)

Targeted High-Throughput Sequencing Identifies Mutations in atlastin-1 as a Cause of Hereditary Sensory Neuropathy Type I Christian Guelly, Peng-Peng.

Haploinsufficiency of TAB2 Causes Congenital Heart Defects in Humans

Reccurrent F8 Intronic Deletion Found in Mild Hemophilia A Causes Alu Exonization Yohann Jourdy, Alexandre Janin, Mathilde Fretigny, Anne Lienhart, Claude.

SCRIB and PUF60 Are Primary Drivers of the Multisystemic Phenotypes of the 8q24.3 Copy-Number Variant Andrew Dauber, Christelle Golzio, Cécile Guenot,

A Nonsense Mutation in DHTKD1 Causes Charcot-Marie-Tooth Disease Type 2 in a Large Chinese Pedigree Wang-yang Xu, Ming-min Gu, Lian-hua Sun, Wen-ting.

Volume 19, Issue 2, Pages (August 2010)

Kindlin-1 Mutant Zebrafish as an In Vivo Model System to Study Adhesion Mechanisms in the Epidermis Ruben Postel, Coert Margadant, Boris Fischer, Maaike.

Mutations in PADI6 Cause Female Infertility Characterized by Early Embryonic Arrest Yao Xu, Yingli Shi, Jing Fu, Min Yu, Ruizhi Feng, Qing Sang, Bo Liang,

Verification of Wild-Type EGFR Status in Non–Small Cell Lung Carcinomas Using a Mutant-Enriched PCR on Selected Cases Yi-Lin Chen, Cheng-Chan Lu, Shu-Ching.

Exome Sequencing Identifies SLC24A5 as a Candidate Gene for Nonsyndromic Oculocutaneous Albinism Ai-Hua Wei, Dong-Jie Zang, Zhe Zhang, Xuan-Zhu Liu,

Mutations in ABCB6 Cause Dyschromatosis Universalis Hereditaria

Volume 19, Issue 19, Pages (October 2009)

Mutations in Multidomain Protein MEGF8 Identify a Carpenter Syndrome Subtype Associated with Defective Lateralization Stephen R.F. Twigg, Deborah Lloyd,

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

Spinal Muscular Atrophy Associated with Progressive Myoclonic Epilepsy Is Caused by Mutations in ASAH1 Jie Zhou, Marcel Tawk, Francesco Danilo Tiziano,

A Recurrent Missense Mutation in ZP3 Causes Empty Follicle Syndrome and Female Infertility Tailai Chen, Yuehong Bian, Xiaoman Liu, Shigang Zhao, Keliang.

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

Activation of a Cryptic Splice Site of PTEN and Loss of Heterozygosity in Benign Skin Lesions in Cowden Disease Stephen J. Meltzer, Manfred Wolter Journal.

RBPJ Mutations Identified in Two Families Affected by Adams-Oliver Syndrome Susan J. Hassed, Graham B. Wiley, Shaofeng Wang, Ji-Yun Lee, Shibo Li, Weihong.

Julien Ablain, Ellen M. Durand, Song Yang, Yi Zhou, Leonard I. Zon

X-Linked Congenital Hypertrichosis Syndrome Is Associated with Interchromosomal Insertions Mediated by a Human-Specific Palindrome near SOX3 Hongwen.

Michaela Floeth, Leena Bruckner-Tuderman

Alexandra Schambony, Doris Wedlich Developmental Cell

Fatema Zahrani, Mohammed A. Aldahmesh, Muneera J. Alshammari, Selwa A

ABCB6 Mutations Cause Ocular Coloboma

The Chemokine SDF1a Coordinates Tissue Migration through the Spatially Restricted Activation of Cxcr7 and Cxcr4b Guillaume Valentin, Petra Haas, Darren.

Identification of a Kir3.4 Mutation in Congenital Long QT Syndrome

Biallelic Mutations in PATL2 Cause Female Infertility Characterized by Oocyte Maturation Arrest Biaobang Chen, Zhihua Zhang, Xiaoxi Sun, Yanping Kuang,

Exome Sequencing and Functional Validation in Zebrafish Identify GTDC2 Mutations as a Cause of Walker-Warburg Syndrome M. Chiara Manzini, Dimira E. Tambunan,

The abcc6a Gene Expression Is Required for Normal Zebrafish Development Qiaoli Li, Sara Sadowski, Michael Frank, Chunli Chai, Andras Váradi, Shiu-Ying.

Mutations in the SPARC-Related Modular Calcium-Binding Protein 1 Gene, SMOC1, Cause Waardenburg Anophthalmia Syndrome Hana Abouzeid, Gaëlle Boisset,

Reccurrent F8 Intronic Deletion Found in Mild Hemophilia A Causes Alu Exonization Yohann Jourdy, Alexandre Janin, Mathilde Fretigny, Anne Lienhart, Claude.

Volume 18, Issue 2, Pages (January 2017)

Identification of 51 Novel Exons of the Usher Syndrome Type 2A (USH2A) Gene That Encode Multiple Conserved Functional Domains and That Are Mutated in.

Julien Ablain, Ellen M. Durand, Song Yang, Yi Zhou, Leonard I. Zon

Exome Sequencing Identifies CCDC8 Mutations in 3-M Syndrome, Suggesting that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human Growth

Arun Kumar, Satish C. Girimaji, Mahesh R. Duvvari, Susan H. Blanton

Zebrafish as a Model Organism for the Identification and Characterization of Drugs and Genes Affecting p53 Signaling Ulrike Langheinrich, Elisabeth Hennen,

Mutations in CHEK2 Associated with Prostate Cancer Risk

CBFβ deficiency leads to heart failure in zebrafish.

Mutations in NEXN, a Z-Disc Gene, Are Associated with Hypertrophic Cardiomyopathy Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao.

PI4K2β/AP-1-Based TGN-Endosomal Sorting Regulates Wnt Signaling

Mutations in POFUT1, Encoding Protein O-fucosyltransferase 1, Cause Generalized Dowling-Degos Disease Ming Li, Ruhong Cheng, Jianying Liang, Heng Yan,

GDF6, a Novel Locus for a Spectrum of Ocular Developmental Anomalies

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

Gene Augmentation and Readthrough Rescue Channelopathy in an iPSC-RPE Model of Congenital Blindness Pawan K. Shahi, Dalton Hermans, Divya Sinha, Simran.

Asaf Ta-Shma, Tahir N. Khan, Asaf Vivante, Jason R

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

Identification of Novel pro-α2(IX) Collagen Gene Mutations in Two Families with Distinctive Oligo-Epiphyseal Forms of Multiple Epiphyseal Dysplasia Paul.

Zhimiao Lin, Quan Chen, Lei Shi, Mingyang Lee, Kathrin A

Presentation transcript:

ABCB6 Mutations Cause Ocular Coloboma Lejing Wang, Fei He, Juan Bu, Xiaqi Liu, Wei Du, Jiamei Dong, Jeffrey D. Cooney, Sushil Kumar Dubey, Yi Shi, Bo Gong, Jing Li, Paul F. McBride, Yanlei Jia, Fang Lu, Kathleen A. Soltis, Ying Lin, Prasanthi Namburi, Chen Liang, Periasamy Sundaresan, Barry H. Paw, Dean Y. Li, John D. Phillips, Zhenglin Yang The American Journal of Human Genetics Volume 90, Issue 1, Pages 40-48 (January 2012) DOI: 10.1016/j.ajhg.2011.11.026 Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 1 Mutations in ABCB6 and Clinical Photographs of Patients with Coloboma (A) Pedigree and segregation of the Leu811Val mutation in the Chinese family affected by coloboma. (B–E) Photographs of patients with coloboma are compared to those of the unaffected individual. The proband (II:5) of the Chinese family has iris coloboma in the lower papillary margin (C) and inferior chorioretinal coloboma (E). Photographs of the normal iris (B) and fundus (D) of the unaffected individual (II:9) in the same family are also shown. (F–H) Two mutations in ABCB6 and their sequencing tracing, including Leu811Val (F) in the Chinese family affected by coloboma and Ala57Thr (G) in the three Indian patients who have microphthalmia and coloboma. A partial sequence of ABCB6 was compared with other species' orthologs (H). Arrows indicate the location of the two mutations identified in patients with ocular coloboma. The American Journal of Human Genetics 2012 90, 40-48DOI: (10.1016/j.ajhg.2011.11.026) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 2 Subcellular Localization of ABCB6 in RPE Cells Immunofluorescent images of the RPE cell that transiently expresses Myc-tagged ABCB6 and markers for subcellular compartments are shown. Neither WT nor mutant ABCB6, both in green, colocalized with a mitochondrial maker, in red (A). Both WT and mutant ABCB6, in green, colocalized with an ER marker, in red (B), and with a Golgi maker, in red (C). The American Journal of Human Genetics 2012 90, 40-48DOI: (10.1016/j.ajhg.2011.11.026) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 3 Expression of ABCB6 in Cell Lines and Tissues and Whole-Mount RNA In Situ Hybridization in Zebrafish (A) RT-PCR analyses of ABCB6 expression in D407 and HEK 293 cells and the human spleen, lungs, kidneys, heart, and blood gave a 435 bp product. β-Actin was used as an internal control for cDNA quantification and gave a 285 bp product. (B) Dorsal views of embryos from 24–72 hpf are shown. WT (unstained) embryos were used as controls. The transcript for abcb6 was expressed in developing CNS tissue, including the eyes, at 24 hpf and later stages. The expression of abcb6 is detected circumferentially around the lens at 36 and 48 hpf. In addition, abcb6 is expressed in developing pectoral fins. The American Journal of Human Genetics 2012 90, 40-48DOI: (10.1016/j.ajhg.2011.11.026) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 4 Zebrafish Eye Development Disturbed by Knockdown of abcb6 Expression and Rescue of abcb6 Morphants (A) RT-PCR verified that abcb6MO2 altered normal abcb6 splicing by deleting exon 2. This deletion results in an abnormal 268 bp product as opposed to a normal 818 bp product. (B) Immunoblotting with the Myc antibody verified that equal amounts of abcb6 produced from the WT and mutant ABCB6 mRNA were coinjected with MOs in zebrafish. β-Actin was used as an internal control. (C–L) Compared with zebrafish embryos treated with standard control MOs (C and D), zebrafish embryos treated with abcb6MO2 show coloboma and retarded development in 96 hpf (E and F). These phenotypes can be rescued by the coinjection of WT ABCB6 mRNA (G and H), but the phenotypes could not be rescued by coinjection of the human mRNA containing either the Leu811Val (I and J) or the Ala57Thr (K and L) mutation. (M) Graph depicting the proportions of embryos with coloboma associated with the injection of either abcb6MO1 or abcb6MO2 and the proportions rescued by coinjection with WT and mutant ABCB6 mRNA. The American Journal of Human Genetics 2012 90, 40-48DOI: (10.1016/j.ajhg.2011.11.026) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 5 Iris Coloboma Produced by Morpholino Knockdown of abcb6 in Zebrafish Compared with the Patients with Coloboma in the Chinese Family (A) A normal iris is shown in an unaffected individual in the same family as the control. (B) A pupil shaped like a keyhole is seen in an affected patient in the Chinese family afflicted with coloboma. (C) The eye of a fish that was treated with a control morpholino. (D) Morphants treated with abcb6MO1 result in a keyhole-shaped pupil similar to that seen in the patients with coloboma. The American Journal of Human Genetics 2012 90, 40-48DOI: (10.1016/j.ajhg.2011.11.026) Copyright © 2012 The American Society of Human Genetics Terms and Conditions