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145 results on '"Bujakowska Kinga M"'

1. Substitution of a single non-coding nucleotide upstream of TMEM216 causes non-syndromic retinitis pigmentosa and is associated with reduced TMEM216 expression

Author

Malka, Samantha, Biswas, Pooja, Berry, Anne-Marie, Sangermano, Riccardo, Ullah, Mukhtar, Lin, Siying, D’Antonio, Matteo, Jestin, Aleksandr, Jiao, Xiaodong, Quinodoz, Mathieu, Sullivan, Lori, Gardner, Jessica C, Place, Emily M, Michaelides, Michel, Kaminska, Karolina, Mahroo, Omar A, Schiff, Elena, Wright, Genevieve, Cancellieri, Francesca, Vaclavik, Veronika, Santos, Cristina, Rehman, Atta Ur, Mehrotra, Sudeep, Baig, Hafiz Muhammad Azhar, Iqbal, Muhammad, Ansar, Muhammad, Santos, Luisa Coutinho, Sousa, Ana Berta, Tran, Viet H, Matsui, Hiroko, Bhatia, Anjana, Naeem, Muhammad Asif, Akram, Shehla J, Akram, Javed, Riazuddin, Ayuso, Carmen, Pierce, Eric A, Hardcastle, Alison J, Riazuddin, S Amer, Frazer, Kelly A, Hejtmancik, J Fielding, Rivolta, Carlo, Bujakowska, Kinga M, Arno, Gavin, Webster, Andrew R, and Ayyagari, Radha

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Neurodegenerative, Rare Diseases, Biotechnology, Neurosciences, Human Genome, 2.1 Biological and endogenous factors, African ancestry, South Asian, ancestral allele, ciliopathy, equity of genetic testing, ethnic genetic diversity, gene expression, non-coding genetic variation, retinal dystrophy, retinitis pigmentosa, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome analysis of individuals affected by retinitis pigmentosa (RP) identified two rare nucleotide substitutions at the same genomic location on chromosome 11 (g.61392563 [GRCh38]), 69 base pairs upstream of the start codon of the ciliopathy gene TMEM216 (c.-69G>A, c.-69G>T [GenBank: NM_001173991.3]), in individuals of South Asian and African ancestry, respectively. Genotypes included 71 homozygotes and 3 mixed heterozygotes in trans with a predicted loss-of-function allele. Haplotype analysis showed single-nucleotide variants (SNVs) common across families, suggesting ancestral alleles within the two distinct ethnic populations. Clinical phenotype analysis of 62 available individuals from 49 families indicated a similar clinical presentation with night blindness in the first decade and progressive peripheral field loss thereafter. No evident systemic ciliopathy features were noted. Functional characterization of these variants by luciferase reporter gene assay showed reduced promotor activity. Nanopore sequencing confirmed the lower transcription of the TMEM216 c.-69G>T allele in blood-derived RNA from a heterozygous carrier, and reduced expression was further recapitulated by qPCR, using both leukocytes-derived RNA of c.-69G>T homozygotes and total RNA from genome-edited hTERT-RPE1 cells carrying homozygous TMEM216 c.-69G>A. In conclusion, these variants explain a significant proportion of unsolved cases, specifically in individuals of African ancestry, suggesting that reduced TMEM216 expression might lead to abnormal ciliogenesis and photoreceptor degeneration.

Published
2024

2. Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration

Author

Sangermano, Riccardo, Gupta, Priya, Price, Cherrell, Han, Jinu, Navarro, Julien, Condroyer, Christel, Place, Emily M., Antonio, Aline, Mukai, Shizuo, Zanlonghi, Xavier, Sahel, José-Alain, DiTroia, Stephanie, O’Heir, Emily, Duncan, Jacque L., Pierce, Eric A., Zeitz, Christina, Audo, Isabelle, Huckfeldt, Rachel M., and Bujakowska, Kinga M.

Published
2024
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4. Exome copy number variant detection, analysis, and classification in a large cohort of families with undiagnosed rare genetic disease

Author

Lemire, Gabrielle, Sanchis-Juan, Alba, Russell, Kathryn, Baxter, Samantha, Chao, Katherine R., Singer-Berk, Moriel, Groopman, Emily, Wong, Isaac, England, Eleina, Goodrich, Julia, Pais, Lynn, Austin-Tse, Christina, DiTroia, Stephanie, O’Heir, Emily, Ganesh, Vijay S., Wojcik, Monica H., Evangelista, Emily, Snow, Hana, Osei-Owusu, Ikeoluwa, Fu, Jack, Singh, Mugdha, Mostovoy, Yulia, Huang, Steve, Garimella, Kiran, Kirkham, Samantha L., Neil, Jennifer E., Shao, Diane D., Walsh, Christopher A., Argilli, Emanuela, Le, Carolyn, Sherr, Elliott H., Gleeson, Joseph G., Shril, Shirlee, Schneider, Ronen, Hildebrandt, Friedhelm, Sankaran, Vijay G., Madden, Jill A., Genetti, Casie A., Beggs, Alan H., Agrawal, Pankaj B., Bujakowska, Kinga M., Place, Emily, Pierce, Eric A., Donkervoort, Sandra, Bönnemann, Carsten G., Gallacher, Lyndon, Stark, Zornitza, Tan, Tiong Yang, White, Susan M., Töpf, Ana, Straub, Volker, Fleming, Mark D., Pollak, Martin R., Õunap, Katrin, Pajusalu, Sander, Donald, Kirsten A., Bruwer, Zandre, Ravenscroft, Gianina, Laing, Nigel G., MacArthur, Daniel G., Rehm, Heidi L., Talkowski, Michael E., Brand, Harrison, and O’Donnell-Luria, Anne

Published
2024
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5. Heterozygous loss-of-function SMC3 variants are associated with variable growth and developmental features

Author

Ansari, Morad, Faour, Kamli N.W., Shimamura, Akiko, Grimes, Graeme, Kao, Emeline M., Denhoff, Erica R., Blatnik, Ana, Ben-Isvy, Daniel, Wang, Lily, Helm, Benjamin M., Firth, Helen, Breman, Amy M., Bijlsma, Emilia K., Iwata-Otsubo, Aiko, de Ravel, Thomy J.L., Fusaro, Vincent, Fryer, Alan, Nykamp, Keith, Stühn, Lara G., Haack, Tobias B., Korenke, G. Christoph, Constantinou, Panayiotis, Bujakowska, Kinga M., Low, Karen J., Place, Emily, Humberson, Jennifer, Napier, Melanie P., Hoffman, Jessica, Juusola, Jane, Deardorff, Matthew A., Shao, Wanqing, Rockowitz, Shira, Krantz, Ian, Kaur, Maninder, Raible, Sarah, Dortenzio, Victoria, Kliesch, Sabine, Singer-Berk, Moriel, Groopman, Emily, DiTroia, Stephanie, Ballal, Sonia, Srivastava, Siddharth, Rothfelder, Kathrin, Biskup, Saskia, Rzasa, Jessica, Kerkhof, Jennifer, McConkey, Haley, Sadikovic, Bekim, Hilton, Sarah, Banka, Siddharth, Tüttelmann, Frank, Conrad, Donald F., O’Donnell-Luria, Anne, Talkowski, Michael E., FitzPatrick, David R., and Boone, Philip M.

Published
2024
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6. Non-syndromic Retinal Degeneration Caused by Pathogenic Variants in Joubert Syndrome Genes

Author

Sangermano, Riccardo, Galdikaité-Braziené, Egle, Bujakowska, Kinga M., Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Steinlein, Ortrud, Series Editor, Xiao, Junjie, Series Editor, Ash, John D., editor, Pierce, Eric, editor, Anderson, Robert E., editor, Bowes Rickman, Catherine, editor, Hollyfield, Joe G., editor, and Grimm, Christian, editor

Published
2023
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7. Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases

Author

Audo Isabelle, Bujakowska Kinga M, Léveillard Thierry, Mohand-Saïd Saddek, Lancelot Marie-Elise, Germain Aurore, Antonio Aline, Michiels Christelle, Saraiva Jean-Paul, Letexier Mélanie, Sahel José-Alain, Bhattacharya Shomi S, and Zeitz Christina

Subjects
NGS, retinal disorders, diagnostic tool., Medicine
Abstract

Abstract Background Inherited retinal disorders are clinically and genetically heterogeneous with more than 150 gene defects accounting for the diversity of disease phenotypes. So far, mutation detection was mainly performed by APEX technology and direct Sanger sequencing of known genes. However, these methods are time consuming, expensive and unable to provide a result if the patient carries a new gene mutation. In addition, multiplicity of phenotypes associated with the same gene defect may be overlooked. Methods To overcome these challenges, we designed an exon sequencing array to target 254 known and candidate genes using Agilent capture. Subsequently, 20 DNA samples from 17 different families, including four patients with known mutations were sequenced using Illumina Genome Analyzer IIx next-generation-sequencing (NGS) platform. Different filtering approaches were applied to identify the genetic defect. The most likely disease causing variants were analyzed by Sanger sequencing. Co-segregation and sequencing analysis of control samples validated the pathogenicity of the observed variants. Results The phenotype of the patients included retinitis pigmentosa, congenital stationary night blindness, Best disease, early-onset cone dystrophy and Stargardt disease. In three of four control samples with known genotypes NGS detected the expected mutations. Three known and five novel mutations were identified in NR2E3, PRPF3, EYS, PRPF8, CRB1, TRPM1 and CACNA1F. One of the control samples with a known genotype belongs to a family with two clinical phenotypes (Best and CSNB), where a novel mutation was identified for CSNB. In six families the disease associated mutations were not found, indicating that novel gene defects remain to be identified. Conclusions In summary, this unbiased and time-efficient NGS approach allowed mutation detection in 75% of control cases and in 57% of test cases. Furthermore, it has the possibility of associating known gene defects with novel phenotypes and mode of inheritance.

Published
2012
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8. Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy.

Author

Cogné, Benjamin, Latypova, Xenia, Senaratne, Lokuliyanage Dona Samudita, Martin, Ludovic, Koboldt, Daniel C, Kellaris, Georgios, Fievet, Lorraine, Le Meur, Guylène, Caldari, Dominique, Debray, Dominique, Nizon, Mathilde, Frengen, Eirik, Bowne, Sara J, 99 Lives Consortium, Cadena, Elizabeth L, Daiger, Stephen P, Bujakowska, Kinga M, Pierce, Eric A, Gorin, Michael, Katsanis, Nicholas, Bézieau, Stéphane, Petersen-Jones, Simon M, Occelli, Laurence M, Lyons, Leslie A, Legeai-Mallet, Laurence, Sullivan, Lori S, Davis, Erica E, and Isidor, Bertrand

Subjects
Lives Consortium, Retina, Cilia, Animals, Zebrafish, Cats, Humans, Rhodopsin, Pedigree, Amino Acid Sequence, Larva, Heterozygote, Genes, Dominant, Phenotype, Mutation, Middle Aged, Child, Preschool, Female, Male, Photoreceptor Cells, Genome-Wide Association Study, Young Adult, Ciliopathies, Kinesins, KIF3B, feline genetics, hepatic fibrosis, kinesin, primary cilia, retinopathy, whole-exome sequencing, zebrafish, Neurosciences, Clinical Research, Genetics, Pediatric, Polycystic Kidney Disease, Eye Disease and Disorders of Vision, Congenital Structural Anomalies, Neurodegenerative, Kidney Disease, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Eye, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous KIF3B variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G>C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by KIF3B. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T>C (p.Leu523Pro) KIF3B variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length in vitro in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of KIF3B mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive KIF3B models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G>A (p.Ala334Thr) KIF3B variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and in vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.

Published
2020

9. Fundamentals of Genetics

Author

Bujakowska, Kinga M., Dryja, Thaddeus P., Comander, Jason, Section editor, Vandenberghe, Luk, Section editor, Albert, Daniel M., editor, Miller, Joan W., editor, Azar, Dimitri T., editor, and Young, Lucy H., editor

Published
2022
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10. The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK)

Author

Zampaglione, Erin, Maher, Matthew, Place, Emily M., Wagner, Naomi E., DiTroia, Stephanie, Chao, Katherine R., England, Eleina, CMG, Broad, Catomeris, Andrew, Nassiri, Sherwin, Himes, Seraphim, Pagliarulo, Joey, Ferguson, Charles, Galdikaité-Braziené, Eglé, Cole, Brian, Pierce, Eric A., and Bujakowska, Kinga M.

Published
2022
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11. Genome Sequencing for Diagnosing Rare Diseases

Author

Wojcik, Monica H., primary, Lemire, Gabrielle, additional, Berger, Eva, additional, Zaki, Maha S., additional, Wissmann, Mariel, additional, Win, Wathone, additional, White, Susan M., additional, Weisburd, Ben, additional, Wieczorek, Dagmar, additional, Waddell, Leigh B., additional, Verboon, Jeffrey M., additional, VanNoy, Grace E., additional, Töpf, Ana, additional, Tan, Tiong Yang, additional, Syrbe, Steffen, additional, Strehlow, Vincent, additional, Straub, Volker, additional, Stenton, Sarah L., additional, Snow, Hana, additional, Singer-Berk, Moriel, additional, Silver, Josh, additional, Shril, Shirlee, additional, Seaby, Eleanor G., additional, Schneider, Ronen, additional, Sankaran, Vijay G., additional, Sanchis-Juan, Alba, additional, Russell, Kathryn A., additional, Reinson, Karit, additional, Ravenscroft, Gianina, additional, Radtke, Maximilian, additional, Popp, Denny, additional, Polster, Tilman, additional, Platzer, Konrad, additional, Pierce, Eric A., additional, Place, Emily M., additional, Pajusalu, Sander, additional, Pais, Lynn, additional, Õunap, Katrin, additional, Osei-Owusu, Ikeoluwa, additional, Opperman, Henry, additional, Okur, Volkan, additional, Oja, Kaisa Teele, additional, O’Leary, Melanie, additional, O’Heir, Emily, additional, Morel, Chantal F., additional, Merkenschlager, Andreas, additional, Marchant, Rhett G., additional, Mangilog, Brian E., additional, Madden, Jill A., additional, MacArthur, Daniel, additional, Lovgren, Alysia, additional, Lerner-Ellis, Jordan P., additional, Lin, Jasmine, additional, Laing, Nigel, additional, Hildebrandt, Friedhelm, additional, Hentschel, Julia, additional, Groopman, Emily, additional, Goodrich, Julia, additional, Gleeson, Joseph G., additional, Ghaoui, Roula, additional, Genetti, Casie A., additional, Gburek-Augustat, Janina, additional, Gazda, Hanna T., additional, Ganesh, Vijay S., additional, Ganapathi, Mythily, additional, Gallacher, Lyndon, additional, Fu, Jack M., additional, Evangelista, Emily, additional, England, Eleina, additional, Donkervoort, Sandra, additional, DiTroia, Stephanie, additional, Cooper, Sandra T., additional, Chung, Wendy K., additional, Christodoulou, John, additional, Chao, Katherine R., additional, Cato, Liam D., additional, Bujakowska, Kinga M., additional, Bryen, Samantha J., additional, Brand, Harrison, additional, Bönnemann, Carsten G., additional, Beggs, Alan H., additional, Baxter, Samantha M., additional, Bartolomaeus, Tobias, additional, Agrawal, Pankaj B., additional, Talkowski, Michael, additional, Austin-Tse, Christina, additional, Abou Jamra, Rami, additional, Rehm, Heidi L., additional, and O’Donnell-Luria, Anne, additional

Published
2024
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13. Detection of Large Structural Variants Causing Inherited Retinal Diseases

Author

Daiger, Stephen P., Sullivan, Lori S., Bowne, Sara J., Cadena, Elizabeth D., Koboldt, Dan, Bujakowska, Kinga M., Pierce, Eric A., Crusio, Wim E., Series Editor, Lambris, John D., Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Bowes Rickman, Catherine, editor, Grimm, Christian, editor, Anderson, Robert E., editor, Ash, John D., editor, LaVail, Matthew M., editor, and Hollyfield, Joe G., editor

Published
2019
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14. Broadening INPP5E phenotypic spectrum: detection of rare variants in syndromic and non-syndromic IRD

Author

Sangermano, Riccardo, Deitch, Iris, Peter, Virginie G., Ba-Abbad, Rola, Place, Emily M., Zampaglione, Erin, Wagner, Naomi E., Fulton, Anne B., Coutinho-Santos, Luisa, Rosin, Boris, Dunet, Vincent, AlTalbishi, Ala’a, Banin, Eyal, Sousa, Ana Berta, Neves, Mariana, Larson, Anna, Quinodoz, Mathieu, Michaelides, Michel, Ben-Yosef, Tamar, Pierce, Eric A., Rivolta, Carlo, Webster, Andrew R., Arno, Gavin, Sharon, Dror, Huckfeldt, Rachel M., and Bujakowska, Kinga M.

Published
2021
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17. Exome copy number variant detection, analysis and classification in a large cohort of families with undiagnosed rare genetic disease

Author

Lemire, Gabrielle, primary, Sanchis-Juan, Alba, additional, Russell, Kathryn, additional, Baxter, Samantha, additional, Chao, Katherine R., additional, Singer-Berk, Moriel, additional, Groopman, Emily, additional, Wong, Isaac, additional, England, Eleina, additional, Goodrich, Julia, additional, Pais, Lynn, additional, Austin-Tse, Christina, additional, DiTroia, Stephanie, additional, O’Heir, Emily, additional, Ganesh, Vijay S., additional, Wojcik, Monica H., additional, Evangelista, Emily, additional, Snow, Hana, additional, Osei-Owusu, Ikeoluwa, additional, Fu, Jack, additional, Singh, Mugdha, additional, Mostovoy, Yulia, additional, Huang, Steve, additional, Garimella, Kiran, additional, Kirkham, Samantha L., additional, Neil, Jennifer E., additional, Shao, Diane D., additional, Walsh, Christopher A., additional, Argili, Emanuela, additional, Le, Carolyn, additional, Sherr, Elliott H., additional, Gleeson, Joseph, additional, Shril, Shirlee, additional, Schneider, Ronen, additional, Hildebrandt, Friedhelm, additional, Sankaran, Vijay G., additional, Madden, Jill A., additional, Genetti, Casie A., additional, Beggs, Alan H., additional, Agrawal, Pankaj B., additional, Bujakowska, Kinga M., additional, Place, Emily, additional, Pierce, Eric A., additional, Donkervoort, Sandra, additional, Bönnemann, Carsten G., additional, Gallacher, Lyndon, additional, Stark, Zornitza, additional, Tan, Tiong, additional, White, Susan M., additional, Töpf, Ana, additional, Straub, Volker, additional, Fleming, Mark D., additional, Pollak, Martin R., additional, Õunap, Katrin, additional, Pajusalu, Sander, additional, Donald, Kirsten A., additional, Bruwer, Zandre, additional, Ravenscroft, Gianina, additional, Laing, Nigel G., additional, MacArthur, Daniel G., additional, Rehm, Heidi L., additional, Talkowski, Michael E., additional, Brand, Harrison, additional, and O’Donnell-Luria, Anne, additional

Published
2023
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18. Heterozygous loss-of-functionSMC3variants are associated with variable and incompletely penetrant growth and developmental features

Author

Ansari, Morad, primary, Faour, Kamli N. W., additional, Shimamura, Akiko, additional, Grimes, Graeme, additional, Kao, Emeline M., additional, Denhoff, Erica R., additional, Blatnik, Ana, additional, Ben-Isvy, Daniel, additional, Wang, Lily, additional, Helm, Benjamin M., additional, Firth, Helen, additional, Breman, Amy M., additional, Bijlsma, Emilia K., additional, Iwata-Otsubo, Aiko, additional, de Ravel, Thomy J.L., additional, Fusaro, Vincent, additional, Fryer, Alan, additional, Nykamp, Keith, additional, Stuhn, Lara G., additional, Haack, Tobias B., additional, Korenke, G. Christoph, additional, Constantinou, Panayiotis, additional, Bujakowska, Kinga M., additional, Low, Karen J., additional, Place, Emily, additional, Humberson, Jennifer, additional, Napier, Melanie P., additional, Hoffman, Jessica, additional, Juusola, Jane, additional, Deardorff, Matthew A., additional, Shao, Wanqing, additional, Rockowitz, Shira, additional, Krantz, Ian, additional, Kaur, Maninder, additional, Raible, Sarah, additional, Kliesch, Sabine, additional, Singer-Berk, Moriel, additional, Groopman, Emily, additional, DiTroia, Stephanie, additional, Ballal, Sonia, additional, Srivastava, Siddharth, additional, Rothfelder, Kathrin, additional, Biskup, Saskia, additional, Rzasa, Jessica, additional, Kerkhof, Jennifer, additional, McConkey, Haley, additional, O'Donnell-Luria, Anne, additional, Sadikovic, Bekim, additional, Hilton, Sarah, additional, Banka, Siddharth, additional, Tuttelmann, Frank, additional, Conrad, Donald F., additional, Talkowski, Michael E., additional, FitzPatrick, David R., additional, and Boone, Philip M., additional

Published
2023
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19. Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis

Author

Wojcik, Monica H, primary, Lemire, Gabrielle, additional, Zaki, Maha S, additional, Wissmann, Mariel, additional, Win, Wathone, additional, White, Sue, additional, Weisburd, Ben, additional, Waddell, Leigh B, additional, Verboon, Jeffrey M, additional, VanNoy, Grace E, additional, Topf, Ana, additional, Tan, Tiong Yang, additional, Straub, Volker, additional, Stenton, Sarah L, additional, Snow, Hana, additional, Singer-Berk, Moriel, additional, Silver, Josh, additional, Shril, Shirlee, additional, Seaby, Eleanor G, additional, Schneider, Ronen, additional, Sankaran, Vijay G, additional, Sanchis-Juan, Alba, additional, Russell, Kathryn A, additional, Reinson, Karit, additional, Ravenscroft, Gina, additional, Pierce, Eric A, additional, Place, Emily M, additional, Pajusalu, Sander, additional, Pais, Lynn, additional, Ounap, Katrin, additional, Osei-Owusu, Ikeoluwa, additional, Okur, Volkan, additional, Oja, Kaisa Teele, additional, OLeary, Melanie, additional, OHeir, Emily, additional, Morel, Chantal, additional, Marchant, Rhett G, additional, Mangilog, Brian E, additional, Madden, Jill A, additional, MacArthur, Daniel, additional, Lovgren, Alysia, additional, Lerner-Ellis, Jordan P, additional, Lin, Jasmine, additional, Laing, Nigel, additional, Hildebrandt, Friedhelm, additional, Groopman, Emily, additional, Goodrich, Julia, additional, Gleeson, Joseph G, additional, Ghaoui, Roula, additional, Genetti, Casie A, additional, Gazda, Hanna, additional, Ganesh, Vijay S, additional, Ganapathi, Mythily, additional, Gallacher, Lyndon, additional, Fu, Jack, additional, Evangelista, Emily, additional, England, Eleina, additional, Donkervoort, Sandra, additional, DiTroia, Stephanie, additional, Cooper, Sandra T, additional, Chung, Wendy K, additional, Christodoulou, John, additional, Chao, Katherine R, additional, Cato, Liam D, additional, Bujakowska, Kinga M, additional, Bryen, Samantha J, additional, Brand, Harrison, additional, Bonnemann, Carsten, additional, Beggs, Alan H, additional, Baxter, Samantha M, additional, Agrawal, Pankaj B, additional, Talkowski, Michael, additional, Austin-Tse, Christina, additional, Rehm, Heidi L, additional, and ODonnell-Luria, Anne, additional

Published
2023
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22. Contributors

Author

Abdel-Rahman, Mohamed H., primary, Au, Elizabeth D., additional, Brantley, Milam A., additional, Bujakowska, Kinga M., additional, Cebulla, Colleen M., additional, Chen, Rui, additional, Cooke Bailey, Jessica N., additional, Davidorf, Frederick H., additional, de Jong, Eiko K., additional, den Hollander, Anneke I., additional, Dharmat, Rachayata, additional, Dhooge, Patty P.A., additional, Farkas, Michael H., additional, Fatehchand, Kavin, additional, Fingert, John H., additional, Gao, Xiaoyi Raymond, additional, Geerlings, Maartje J., additional, Haines, Jonathan L., additional, Hoyng, Carel B., additional, Igo, Robert P., additional, Isildak, Hacer, additional, Kaczynski, Tadeusz J., additional, Khaled, Mariam Lotfy, additional, Liu, Yutao, additional, Main, Leighanne R., additional, Miller, Matthew A, additional, Ohr, Matthew P., additional, Pilarski, Robert, additional, Place, Emily, additional, Punzo, Claudio, additional, Sangermano, Riccardo, additional, Schwartz, Stephen G., additional, Scott, Hilary, additional, Sui, Ruifang, additional, Valkenburg, Dyon, additional, van der Heide, Carly J., additional, Wagner, Naomi, additional, Waksmunski, Andrea R., additional, Wang, Hui, additional, Weihbrecht, Katie, additional, and Youngblood, Hannah, additional

Published
2020
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27. Panel-based genetic diagnostic testing for inherited eye diseases is highly accurate and reproducible, and more sensitive for variant detection, than exome sequencing

Author

Consugar, Mark B., Navarro-Gomez, Daniel, Place, Emily M., Bujakowska, Kinga M., Sousa, Maria E., Fonseca-Kelly, Zoë D., Taub, Daniel G., Janessian, Maria, Wang, Dan Yi, Au, Elizabeth D., Sims, Katherine B., Sweetser, David A., Fulton, Anne B., Liu, Qin, Wiggs, Janey L., Gai, Xiaowu, and Pierce, Eric A.

Published
2015
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28. Identification of a novel large multigene deletion and a frameshift indel inPDE6Bas the underlying cause of early-onset recessive rod–cone degeneration

Author

Sangermano, Riccardo, primary, Biswas, Pooja, additional, Sullivan, Lori S., additional, Place, Emily M., additional, Borooah, Shyamanga, additional, Straubhaar, Juerg, additional, Pierce, Eric A., additional, Daiger, Stephen P., additional, Bujakowska, Kinga M., additional, and Ayaggari, Radha, additional

Published
2022
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32. Identification of a novel large multigene deletion and a frameshift indel in PDE6B as the underlying cause of early-onset recessive rod-cone degeneration.

Author

Sangermano, Riccardo, Biswas, Pooja, Sullivan, Lori S., Place, Emily M., Borooah, Shyamanga, Straubhaar, Juerg, Pierce, Eric A., Daiger, Stephen P., Bujakowska, Kinga M., and Ayaggari, Radha

Subjects
FRAMESHIFT mutation, RETINAL degeneration, GENETIC disorders, CONGENITAL disorders, PERIPHERAL vision
Abstract

A family, with two affected identical twins with early-onset recessive inherited retinal degeneration, was analyzed to determine the underlying genetic cause of pathology. Exome sequencing revealed a rare and previously reported causative variant (c.1923_1969delinsTCTGGG; p.Asn643Glyfs*29) in the PDE6B gene in the affected twins and their unaffected father. Further investigation, using genome sequencing, identified a novel ~7.5-kb deletion (Chr 4:670,405-677,862del) encompassing the ATP5ME gene, part of the 5' UTR of MYL5, and a 378-bp (Chr 4:670,405-670,782) region from the 3' UTR of PDE6B in the affected twins and their unaffected mother. Both variants segregated with disease in the family. Analysis of the relative expression of PDE6B, in peripheral blood cells, also revealed a significantly lower level of PDE6B transcript in affected siblings compared to a normal control. PDE6B is associated with recessive rod-cone degeneration and autosomal dominant congenital stationary night blindness. Ophthalmic evaluation of these patients showed night blindness, fundus abnormalities, and peripheral vision loss, which are consistent with PDE6B-associated recessive retinal degeneration. These findings suggest that the loss of PDE6B transcript resulting from the compound heterozygous pathogenic variants is the underlying cause of recessive rod-cone degeneration in the study family. [ABSTRACT FROM AUTHOR]

Published
2022
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33. Mutations in IFT172 cause isolated retinal degeneration and Bardet–Biedl syndrome

Author

Bujakowska, Kinga M., Zhang, Qi, Siemiatkowska, Anna M., Liu, Qin, Place, Emily, Falk, Marni J., Consugar, Mark, Lancelot, Marie-Elise, Antonio, Aline, Lonjou, Christine, Carpentier, Wassila, Mohand-Saïd, Saddek, den Hollander, Anneke I., Cremers, Frans P.M., Leroy, Bart P., Gai, Xiaowu, Sahel, José-Alain, van den Born, L. Ingeborgh, Collin, Rob W.J., Zeitz, Christina, Audo, Isabelle, and Pierce, Eric A.

Published
2015
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34. Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy

Author

Buckley, Reuben M., Aberdein, Danielle, Alves, Paulo C., Barsh, Gregory S., Bellone, Rebecca R., Bergström, Tomas F., Boyko, Adam R., Brockman, Jeffrey A., Casal, Margret L., Castelhano, Marta G., Distl, Ottmar, Dodman, Nicholas H., Ellinwood, N. Matthew, Fogle, Jonathan E., Forman, Oliver P., Garrick, Dorian J., Ginns, Edward I., Häggström, Jens, Harvey, Robert J., Hasegawa, Daisuke, Haase, Bianca, Helps, Christopher R., Hernandez, Isabel, Hytönen, Marjo K., Kaukonen, Maria, Kaelin, Christopher B., Kosho, Tomoki, Leclerc, Emilie, Lear, Teri L., Leeb, Tosso, Li, Ronald H.L., Lohi, Hannes, Longeri, Maria, Magnuson, Mark A., Malik, Richard, Mane, Shrinivas P., Munday, John S., Murphy, William J., Pedersen, Niels C., Rothschild, Max F., Rusbridge, Clare, Shapiro, Beth, Stern, Joshua A., Swanson, William F., Terio, Karen A., Todhunter, Rory J., Warren, Wesley C., Wilcox, Elizabeth A., Wildschutte, Julia H., Yu, Yoshihiko, Cogné, Benjamin, Latypova, Xenia, Senaratne, Lokuliyanage Dona Samudita, Martin, Ludovic, Koboldt, Daniel C., Kellaris, Georgios, Fievet, Lorraine, Le Meur, Guylène, Caldari, Dominique, Debray, Dominique, Nizon, Mathilde, Frengen, Eirik, Bowne, Sara J., Cadena, Elizabeth L., Daiger, Stephen P., Bujakowska, Kinga M., Pierce, Eric A., Gorin, Michael, Katsanis, Nicholas, Bézieau, Stéphane, Petersen-Jones, Simon M., Occelli, Laurence M., Lyons, Leslie A., Legeai-Mallet, Laurence, Sullivan, Lori S., Davis, Erica E., and Isidor, Bertrand

Published
2020
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35. Contribution of non-coding mutations to RPGRIP1-mediated inherited retinal degeneration

Author

Jamshidi, Farzad, Place, Emily M., Mehrotra, Sudeep, Navarro-Gomez, Daniel, Maher, Mathew, Branham, Kari E., Valkanas, Elise, Cherry, Timothy J., Lek, Monkol, MacArthur, Daniel, Pierce, Eric A., and Bujakowska, Kinga M.

Subjects
Adult, Male, non-coding mutations, Whole Genome Sequencing, inherited retinal degeneration, DNA Mutational Analysis, Retinal Degeneration, intronic mutations, Chromosome Mapping, Proteins, Article, Pedigree, Cytoskeletal Proteins, HEK293 Cells, whole-genome sequencing, Mutation, Exome Sequencing, Humans, DNA, Intergenic, Female, RPGRIP1
Abstract

With the advent of gene therapies for inherited retinal degenerations (IRDs), genetic diagnostics will have an increasing role in clinical decision-making. Yet the genetic cause of disease cannot be identified using exon-based sequencing for a significant portion of patients. We hypothesized that noncoding pathogenic variants contribute significantly to the genetic causality of IRDs and evaluated patients with single coding pathogenic variants in RPGRIP1 to test this hypothesis.IRD families underwent targeted panel sequencing. Unsolved cases were explored by exome and genome sequencing looking for additional pathogenic variants. Candidate pathogenic variants were then validated by Sanger sequencing, quantitative polymerase chain reaction, and in vitro splicing assays in two cell lines analyzed through amplicon sequencing.Among 1722 families, 3 had biallelic loss-of-function pathogenic variants in RPGRIP1 while 7 had a single disruptive coding pathogenic variants. Exome and genome sequencing revealed potential noncoding pathogenic variants in these 7 families. In 6, the noncoding pathogenic variants were shown to lead to loss of function in vitro.Noncoding pathogenic variants were identified in 6 of 7 families with single coding pathogenic variants in RPGRIP1. The results suggest that noncoding pathogenic variants contribute significantly to the genetic causality of IRDs and RPGRIP1-mediated IRDs are more common than previously thought.

Published
2018

38. WDR34 , a candidate gene for non‐syndromic rod‐cone dystrophy

Author

Solaguren‐Beascoa, Maria, primary, Bujakowska, Kinga M., additional, Méjécase, Cécile, additional, Emmenegger, Lisa, additional, Orhan, Elise, additional, Neuillé, Marion, additional, Mohand‐Saïd, Saddek, additional, Condroyer, Christel, additional, Lancelot, Marie‐Elise, additional, Michiels, Christelle, additional, Demontant, Vanessa, additional, Antonio, Aline, additional, Letexier, Mélanie, additional, Saraiva, Jean‐Paul, additional, Lonjou, Christine, additional, Carpentier, Wassila, additional, Léveillard, Thierry, additional, Pierce, Eric A., additional, Dollfus, Hélène, additional, Sahel, José‐Alain, additional, Bhattacharya, Shomi S., additional, Audo, Isabelle, additional, and Zeitz, Christina, additional

Published
2020
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39. Early onset non-syndromic retinal degeneration due to variants in INPP5E: phenotypic expansion of the ciliary gene previously associated with Joubert syndrome

Author

Sangermano, Riccardo, primary, Deitch, Iris, additional, Peter, Virginie G., additional, Ba-Abbad, Rola, additional, Place, Emily M., additional, Wagner, Naomi E., additional, Fulton, Anne B., additional, Coutinho-Santos, Luisa, additional, Rosin, Boris, additional, Dunet, Vincent, additional, AlTalbishi, Ala’a, additional, Banin, Eyal, additional, Sousa, Ana Berta, additional, Neves, Mariana, additional, Larson, Anna, additional, Quinodoz, Mathieu, additional, Michaelides, Michel, additional, Ben-Yosef, Tamar, additional, Pierce, Eric A., additional, Rivolta, Carlo, additional, Webster, Andrew R., additional, Arno, Gavin, additional, Sharon, Dror, additional, Huckfeldt, Rachel M., additional, and Bujakowska, Kinga M., additional

Published
2020
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41. Expanding the phenotypic spectrum in RDH12-associated retinal disease

Author

Scott, Hilary A., primary, Place, Emily M., additional, Ferenchak, Kevin, additional, Zampaglione, Erin, additional, Wagner, Naomi E., additional, Chao, Katherine R., additional, DiTroia, Stephanie P., additional, Navarro-Gomez, Daniel, additional, Mukai, Shizuo, additional, Huckfeldt, Rachel M., additional, Pierce, Eric A., additional, and Bujakowska, Kinga M., additional

Published
2020
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42. Contributors

Author

Abrams, Gary W., Afshar, Armin R., Agarwal, Aniruddha, Agarwal, Anita, Ahmed, Ishrat, Aiello, Lloyd Paul, Ajlan, Radwan S., Albert, Daniel M., Andreoli, Michael T., Arepalli, Sruthi, Aronow, Mary E., Ashraf, Mohamed, Au, Adrian, Ávila, Marcos, Aylward, G. William, Bagger, Mette M., Balaratnasingam, Chandrakumar, Barry, Robert J., Belfort, Rubens, Jr., Bennett, Jean, Berry, Jesse L., Besirli, Cagri G., Bessette, Angela, Bharti, Kapil, Bhende, Muna, Bhende, Pramod S., Binder, Susanne, Binkley, Elaine M., Bird, Alan C., Blumenkranz, Mark S., Boldt, H. Culver, Boon, Camiel Jan Fons, Borrelli, Enrico, Boulton, Michael E., Brantley, Milam A., Jr., Bressler, Neil M., Bressler, Susan B., Bringmann, Andreas, Brinton, Daniel A., Brown, Gary C., Brown, Melissa M., Brunner, Simon, Budoff, Greg, Bujakowska, Kinga M., Canto-Soler, M. Valeria, Cao, Dingcai, Capone, Antonio, Jr., Carroll, Joseph, Carruthers, David, Caspi, Rachel R., Chaikitmongkol, Voraporn, Chan, Hwei Wuen, Chang Chusan, Yuilyn A., Charles, Steve, Charteris, David G., Chen, Jeannie, Chen, Judy J., Cheung, Carol Y., Cheung, Chui Ming Gemmy, Chew, Emily Y., Chhablani, Jay, Chiang, Michael F., Chon, Brian, Clegg, Dennis O., Comander, Jason, Corradetti, Giulia, Coupland, Sarah E., Cozzi, Mariano, Cruess, Alan F., Cunningham, Emmett T., Jr., Curcio, Christine A., Damato, Bertil E., Davis, Janet L., Davoudi, Samaneh, Ghafoori, Shelley Day, Denniston, Alastair K., de Smet, Marc D., Zaeytijd, Julie De, Dhaliwal, Ranjit S., Dick, Andrew D., Ding, Xiaoyan, Do, Diana V., Dugel, Pravin, Duker, Jay S., Dunbar, Hannah M.P., Duncan, Jacque L., Ehlers, Justis P., Eldred, Kiara C., Eliott, Dean, Wardani, Mohamad El, Engelbert, Michael, Faia, Lisa J., Falsini, Benedetto, Fekrat, Sharon, Ferrington, Deborah A., Ferris, Frederick L., III, Finger, Paul T., Fisher, Steven K., Fisher, Yale L., Fishman, Gerald A., Fleckenstein, Monika, Flynn, Harry W., Jr., Francelin, Carolina, Francis, Jasmine H., Freeman, William R., Freund, K. Bailey, Fu, Arthur D., Garcia-Valenzuela, Enrique, Garg, Sunir J., Gaudric, Alain, Gayed, Mary, George, Roshan T., Goldberg, Morton F., Gopal, Lingam, Gordon, Caroline, Goto, Hiroshi, Gragoudas, Evangelos S., Grant, Maria B., Gregg, Ronald G., Gregory-Evans, Kevin, Groenewald, Carl, Grossniklaus, Hans E., Grover, Sandeep, Gullapalli, Vamsi K., Hahn, Paul, Haller, Julia A., Han, Ian C., Handa, James T., Haritoglou, Christos, Haug, Sara, Hawkins, Barbara S., He, Shikun, Heimann, Heinrich, Henderson, Robert H., Herwig-Carl, Martina C., Heussen, Florian M.A., Hisatomi, Toshio, Holder, Graham E., Holz, Frank G., Hou, Kirk K., Hui, Yan-Nian, Humayun, Mark S., Idrees, Sana, Ikuno, Yasushi, Invernizzi, Alessandro, Ip, Michael S., Isaac, David L.C., Ishibashi, Tatsuro, Ishikawa, Keijiro, Jabs, Douglas A., Jaffe, Glenn J., Jager, Martine J., Jampol, Lee M., Jeng-Miller, Karen, Joffe, Leonard, Johnson, Mark, Johnson, Mark W., Johnson, Robert N., Joussen, Antonia M., Jumper, J. Michael, Jung, Jesse J., Kaiser, Peter K., Kamermans, Maarten, Kampik, Anselm, Karanjia, Rustum, Kashani, Amir H., Keane, Pearse A., Kenney, M. Cristina, Kiilgaard, Jens F., Kiliç, Emine, Kim, Ivana K., Kim, Jonathan W., Kim, Leo A., Kim, Stephen J., Kiss, Szilárd, Klufas, Michael A., Konstantinidis, Lazaros, Koronyo-Hamaoui, Maya, Kowluru, Renu, Kozak, Igor, Kuriyan, Ajay E., Lam, Dennis Shun Chiu, Lam, Linda A., Lane, Anne Marie, Lavik, Erin B., Leary, James F., Ledesma-Gil, Gerardo, Lee, Aaron Y., Lee, Richard W., Lee, Sun Young, Lee, Thomas C., Lee, Won Ki, Leung, Loh-Shan B., Lewis, Geoffrey P., Leys, Anita, Li, Xiaoxin, Liakopoulos, Sandra, Lin, Chang-Ping, Lin, Phoebe, Lin, Xihui, Lois, Noemi, London, Nikolas J.S., Luo, Yan, Lutty, Gerard A., MacLaren, Robert E., Maguire, Albert M., Mahroo, Omar A., Mainster, Martin A., Markoe, Arnold M., Marmor, Michael F., Massey, Stephen C., McCall, Maureen A., McCannel, Tara A., McCutchan, J. Allen, McDonald, H. Richard, Meier, Petra, Meredith, Travis A., Meyer, Carsten H., Mieler, William F., Miller, Joan W., Mirza, Rukhsana G., Mittra, Robert A., Montemagno, Carlo, Moore, Anthony T., Mruthyunjaya, Prithvi, Muccioli, Cristina, Mullins, Robert F., Murphree, A. Linn, Murray, Philip I., Murray, Timothy G., Nagiel, Aaron, Nagpal, Manish, Namperumalsamy, Perumalsamy, Nanda, Sumit K., Narala, Ramsudha, Nascimento, Heloisa, Nashine, Sonali, Nguyen, Quan Dong, Oellers, Patrick, Ohji, Masahito, Ohno-Matsui, Kyoko, Palanker, Daniel, Papakostas, Thanos D., Park, Tea Soon, Park, Un Chul, Patel, Purnima S., Patel, Shriji, Pavlick, Anna C., Peereboom, David M., Pellegrini, Marco, Peng, Michelle, Pennesi, Mark E., Pepple, Kathryn L., Perry, Julian D., Pertile, Grazia, Priglinger, Siegfried, Preziosa, Chiara, Pulido, Jose S., Querques, Giuseppe, Quiram, Polly A., Radke, Nishant Vijay, Raja, Vignesh, Raman, Rajiv, Ramchandran, Rajeev S., Rao, Narsing A., Rao, P. Kumar, Rathinam, SR, Raval, Vishal, Reed, David, Reh, Thomas A., Rezaei, Kourous A., Rhodes, Benjamin, Ritch, Robert, Robson, Anthony G., Rodrigues, Eduardo B., Rowan, Sheldon, Rowland, Teisha J., Rubin, Gary S., Sadda, SriniVas R., Sadun, Alfredo A., Sakamoto, Taiji, Sampath, Alapakkam P., Sangave, Amit A., Sarraf, David, Schachat, Andrew P., Schechet, Sidney A., Schmitz-Valckenberg, Steffen, Schwartz, Stephen G., Scott, Adrienne W., Sebag, J., Seddon, Johanna M., Segrè, Ayellet V., Sepah, Yasir Jamal, Sharma, Sanjay, Sharma, Sumit, Sharma, Tarun, Sheu, Shwu-Jiuan, Shields, Carol L., Shields, Jerry A., Shukla, Dhananjay, Sieving, Paul A., Silva, Paolo S., Silverman, Ronald H., Singer, Joshua, Singh, Arun D., Singh, Nakul, Skalet, Alison H., Skugor, Mario, Smith, Sylvia B., Sobrin, Lucia, Sohn, Elliott H., Souied, Eric H., Spaide, Richard F., Spencer, Doran, Spielberg, Leigh, Sridhar, Akshayalakshmi, Srivastava, Sunil K., Starr, Matthew R., Staurenghi, Giovanni, Stern, Marc-Henri, Sternberg, Paul, Jr., Stiefel, Hillary C., Stitt, Alan W., Stone, Edwin M., Strettoi, Enrica, Sugino, Ilene K., Sullivan, Paul, Sun, Jennifer K., Sunness, Janet S., Tadayoni, Ramin, Tang, Shibo, Taylor, Allen, Terasaki, Hiroko, Thompson, John T., Ting, Daniel S.W., Toro, Mario D., Toth, Cynthia A., Toy, Brian, Trese, Michael T., Tsai, Julie H., Tsang, Stephen H., Tufail, Adnan, Tummala, Gayathri, Udar, Nitin, Ueta, Takashi, Ulrich, J. Niklas, Umfress, Allison C., van Dijk, Elon Hendrik Cornelis, van Meurs, Jan C., Vasconcelos-Santos, Daniel Vítor, Vavvas, Demetrios G., Venkat, Arthi, Waheed, Nadia K., Warner, Nathaniel C., Wickham, Louisa, Wiedemann, Peter, Wiley, Henry E., Wilkinson, C.P., Wolf, Sebastian, Wolfensberger, Thomas J., Wong, Tien Yin, Wu, Yue, Yandiev, Yanors, Yang, Chang-Hao, Yang, Chung-May, Yang, Paul, Yeh, Po-Ting, Yonekawa, Yoshihiro, Yoon, Young Hee, Yordi, Sari, Yu, Hyeong Gon, Yue, Lan, Zarbin, Marco A., Zhu, Ivy, and Zinkernagel, Martin

Published
2023
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43. The importance of genetic testing as demonstrated by two cases of CACNA1F-associated retinal generation misdiagnosed as LCA

Author

Men, Clara J., Bujakowska, Kinga M., Comander, Jason, Place, Emily, Bedoukian, Emma C., Zhu, Xiaosong, Leroy, Bart P., Fulton, Anne B., and Pierce, Eric A.

Subjects
Male, genetic structures, Calcium Channels, L-Type, DNA Mutational Analysis, Leber Congenital Amaurosis, High-Throughput Nucleotide Sequencing, Infant, Eye Diseases, Hereditary, Genetic Diseases, X-Linked, Refractive Errors, eye diseases, Nystagmus, Pathologic, Night Blindness, Electroretinography, Myopia, Humans, Point Mutation, Visual Field Tests, Exome, sense organs, Genetic Testing, Diagnostic Errors, Visual Fields, Research Article
Abstract

Purpose To describe in detail cases with an initial diagnosis of Leber congenital amaurosis that were later found to have a hemizygous mutation in the CACNA1F gene. Methods The patients underwent a detailed ophthalmological evaluation and full-field electroretinography (ERG). Selective targeted capture and whole-exome next-generation sequencing (NGS) were used to find the disease-causing mutations. Results Patient 1 presented at age 3 months with nystagmus, normal visual attention, and a normal fundus exam. ERG responses were severely decreased. Patient 2 presented with nystagmus, severe hyperopia, esotropia, and visual acuity of 20/360 oculus dexter (OD) and 20/270 oculus sinister (OS) at age 5 months. His fundus exam showed slightly increased pigmentation around the foveae. The scotopic ERG responses were severely decreased and photopic responses mildly decreased. Based on the initial presentation, both patients received the clinical diagnosis of Leber congenital amaurosis (LCA). However, genetic testing showed no mutations in known LCA genes. Instead, broader genetic testing using NGS showed point mutations in the CACNA1F gene, which is reported to be associated with type 2 congenital stationary night blindness (CSNB2). Conclusions These two cases demonstrate the clinical overlap between LCA and CSNB in infants and young children. Genetic testing is an essential tool in these cases and provides a more accurate diagnosis and prognosis for patients with inherited retinal degenerative disorders.

Published
2017

44. A hidden structural variation in a known IRD gene: a cautionary tale of two new disease candidate genes.

Author

Scott, Hilary A., Larson, Anna, Rong, Shi Song, Mehrotra, Sudeep, Butcher, Rossano, Chao, Katherine R., Wiggs, Janey L., Place, Emily M., Pierce, Eric A., and Bujakowska, Kinga M.

Subjects
DYSTROPHY, CELL lines, EXOMES, BIOINFORMATICS, DNA sequencing
Abstract

Rod-cone dystrophy (RCD), also known as retinitis pigmentosa, is an inherited condition leading to vision loss, affecting 1 in 3500 people. More than 270 genes are known to be implicated in the inherited retinal degenerations (IRDs), yet genetic diagnosis for ~30% of IRD of patients remains elusive despite advances in sequencing technologies. The goal of this study was to determine the genetic causality in a family with RCD. Family members were given a full ophthalmic exam at the Retinal Service at Massachusetts Eye and Ear and consented to genetic testing. Whole-exome sequencing (WES) was performed and variants of interest were Sanger-validated. Functional assays were conducted in zebrafish along with splicing assays in relevant cell lines to determine the impact on retinal function. WES identified variants in two potential candidate genes that segregated with disease: GNL3 (G Protein Nucleolar 3) c.1187 +3A >C and c.1568-8C >A; and PDE4DIP (Phosphodiester 4D Interacting Protein) c.3868G >A (p.Glu1290Lys) and c.4603G >A (p.Ala1535Thr). Both genes were promising candidates based on their retinal involvement (development and interactions with IRD-associated proteins); however, the functional assays did not validate either gene. Subsequent WES reanalysis with an updated bioinformatics pipeline and widened search parameters led to the detection of a 94-bp duplication in PRPF31 (premRNA Processing Factor 31) c.73_266dup (p.Asp56GlyfsTer33) as the causal variant. Our study demonstrates the importance of thorough functional characterization of new disease candidate genes and the value of reanalyzing next-generation sequencing sequence data, which in our case led to identification of a hidden pathogenic variant in a known IRD gene. [ABSTRACT FROM AUTHOR]

Published
2022
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45. A combined RNA-seq and whole genome sequencing approach for identification of non-coding pathogenic variants in single families

Author

Bronstein, Revital, primary, Capowski, Elizabeth E., additional, Mehrotra, Sudeep, additional, Jansen, Alex D., additional, Navarro-Gomez, Daniel, additional, Maher, Mathew, additional, Place, Emily, additional, Sangermano, Riccardo, additional, Bujakowska, Kinga M., additional, Gamm, David M., additional, and Pierce, Eric A., additional

Published
2019
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46. Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations

Author

Zampaglione, Erin, primary, Kinde, Benyam, additional, Place, Emily M., additional, Navarro-Gomez, Daniel, additional, Maher, Matthew, additional, Jamshidi, Farzad, additional, Nassiri, Sherwin, additional, Mazzone, J. Alex, additional, Finn, Caitlin, additional, Schlegel, Dana, additional, Comander, Jason, additional, Pierce, Eric A., additional, and Bujakowska, Kinga M., additional

Published
2019
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47. Longitudinal Clinical Follow-up and Genetic Spectrum of Patients With Rod-Cone Dystrophy Associated With Mutations inPDE6AandPDE6B

Author

Khateb, Samer, primary, Nassisi, Marco, additional, Bujakowska, Kinga M., additional, Méjécase, Cécile, additional, Condroyer, Christel, additional, Antonio, Aline, additional, Foussard, Marine, additional, Démontant, Vanessa, additional, Mohand-Saïd, Saddek, additional, Sahel, José-Alain, additional, Zeitz, Christina, additional, and Audo, Isabelle, additional

Published
2019
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48. WDR34, a candidate gene for non‐syndromic rod‐cone dystrophy.

Author

Solaguren‐Beascoa, Maria, Bujakowska, Kinga M., Méjécase, Cécile, Emmenegger, Lisa, Orhan, Elise, Neuillé, Marion, Mohand‐Saïd, Saddek, Condroyer, Christel, Lancelot, Marie‐Elise, Michiels, Christelle, Demontant, Vanessa, Antonio, Aline, Letexier, Mélanie, Saraiva, Jean‐Paul, Lonjou, Christine, Carpentier, Wassila, Léveillard, Thierry, Pierce, Eric A., Dollfus, Hélène, and Sahel, José‐Alain

Subjects
*HOMOZYGOSITY, *DYSTROPHY, *RETINITIS pigmentosa, *RETINAL degeneration, *GENES, *CILIOPATHY
Abstract

Rod‐cone dystrophy (RCD), also called retinitis pigmentosa, is characterized by rod followed by cone photoreceptor degeneration, leading to gradual visual loss. Mutations in over 65 genes have been associated with non‐syndromic RCD explaining 60% to 70% of cases, with novel gene defects possibly accounting for the unsolved cases. Homozygosity mapping and whole‐exome sequencing applied to a case of autosomal recessive non‐syndromic RCD from a consanguineous union identified a homozygous variant in WDR34. Mutations in WDR34 have been previously associated with severe ciliopathy syndromes possibly associated with a retinal dystrophy. This is the first report of a homozygous mutation in WDR34 associated with non‐syndromic RCD. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Clinical Features of a Retinopathy Associated With a Dominant Allele of the RGR Gene

Author

Ba-Abbad, Rola, primary, Leys, Monique, additional, Wang, Xinjing, additional, Chakarova, Christina, additional, Waseem, Naushin, additional, Carss, Keren J., additional, Raymond, F. Lucy, additional, Bujakowska, Kinga M., additional, Pierce, Eric A., additional, Mahroo, Omar A., additional, Mohamed, Moin D., additional, Holder, Graham E., additional, Hummel, Marybeth, additional, Arno, Gavin, additional, and Webster, Andrew R., additional

Published
2018
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