CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders

Francesco Brancati, Giuseppe Barrano, Jennifer L. Silhavy, Sarah E. Marsh, Lorena Travaglini, Stephanie L. Bielas, Maria Amorini, Dominika Zablocka, Hulya Kayserili, Lihadh Al-Gazali, Enrico Bertini, Eugen Boltshauser, Marc D'Hooghe, Elisa Fazzi, Elif Y. Fenerci, Raoul C M Hennekam, Andrea Kiss, Melissa M. Lees, Elysa Marco, Shubha R. Phadke & 114 others Luciana Rigoli, Stephane Romano, Carmelo D. Salpietro, Elliott H. Sherr, Sabrina Signorini, Petter Stromme, Bernard Stuart, Laszlo Sztriha, David H. Viskochil, Adnan Yuksel, Bruno Dallapiccola, Enza Maria Valente, Joseph G. Gleeson, Padraic Grattan-Smith, Richard Leventer, Andreas Janecke, Rudy Van Coster, Karin Dias, Carla Moco, Ana Moreira, Ae Kim Chong, Gustavo Maegawa, Ghada M H Abdel-Salam, Alice Kamal Abd El Aleem, Maha S. Zaki, Itxaso Marti, Susana Quijano-Roy, Pascale De Lonlay, Alain Verloes, Renaud Touraine, Michel Koenig, Clotilde Lagier-Tourenne, Jean Messer, Heike Philippi, Sofia Kitsiou Tzeli, Saevar Halldorsson, Jonina Johannsdottir, Peter Ludvigsson, Alex Magee, Dorit Lev, Marina Michelson, Bruria Ben-Zeev, Rita Fischetto, Mattia Gentile, Silvia Battaglia, Lucio Giordano, Loredana Boccone, Martino Ruggieri, Stefania Bigoni, Alessandra Ferlini, Maria Alice Donati, Elena Procopio, Gianluca Caridi, Francesca Faravelli, Gianmarco Ghiggeri, Silvana Briuglia, Gaetano Tortorella, Stefano D'Arrigo, Chiara Pantaleoni, Daria Riva, Graziella Uziel, Anna Maria Lavercla, Alberto Permunian, Stefania Bova, Roberta Battini, Maria Roberta Cilio, Marilù Di Sabato, Francesco Emma, Vincenzo Leuzzi, Pasquale Parisi, Alessandro Simonati, Asma A. Al-Tawari, Laila Bastaki, Ahmad Aqeel, Mirjam M. De Jong, Roshan Koul, Anna Rajab, Matloob Azam, Clara Barbot, Berta Rodriguez, Ignacio Pascual-Castroviejo, Sinan Comu, Mustafa Akcakus, David Nicholl, C. Geoffrey Woods, Christopher Bennett, Jane Hurst, Christopher A. Walsh, Saunder Bernes, Henry Sanchez, Aldon E. Clark, Clement Donahue, Jin Hahn, Terence D. Sanger, Tomas E. Gallager, William B. Dobyns, Cynthia Daugherty, Kalpathy S. Krishnamoorthy, Dean Sarco, Trudy McKanna, Joanne Milisa, Wendy K. Chung, Darryl C. De Vivo, Hillary Raynes, Romaine Schubert, Alison Seward, David G. Brooks, Amy Goldstein, James Caldwell, Eco Finsecke, Bernard L. Maria, Kenton Holden, Robert P. Cruse, Kathryn J. Swoboda

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MPS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Löken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.

Original languageEnglish
Pages (from-to)104-113
Number of pages10
JournalAmerican Journal of Human Genetics
Volume81
Issue number1
DOIs
Publication statusPublished - Jul 2007
Externally publishedYes

Fingerprint

Kidney
Mutation
Eye Manifestations
Situs Inversus
Rhombencephalon
Mesencephalon
Joubert syndrome 1
Neuroimaging
Tooth
Phenotype
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Brancati, F., Barrano, G., Silhavy, J. L., Marsh, S. E., Travaglini, L., Bielas, S. L., ... Swoboda, K. J. (2007). CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. American Journal of Human Genetics, 81(1), 104-113. https://doi.org/10.1086/519026

CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. / Brancati, Francesco; Barrano, Giuseppe; Silhavy, Jennifer L.; Marsh, Sarah E.; Travaglini, Lorena; Bielas, Stephanie L.; Amorini, Maria; Zablocka, Dominika; Kayserili, Hulya; Al-Gazali, Lihadh; Bertini, Enrico; Boltshauser, Eugen; D'Hooghe, Marc; Fazzi, Elisa; Fenerci, Elif Y.; Hennekam, Raoul C M; Kiss, Andrea; Lees, Melissa M.; Marco, Elysa; Phadke, Shubha R.; Rigoli, Luciana; Romano, Stephane; Salpietro, Carmelo D.; Sherr, Elliott H.; Signorini, Sabrina; Stromme, Petter; Stuart, Bernard; Sztriha, Laszlo; Viskochil, David H.; Yuksel, Adnan; Dallapiccola, Bruno; Valente, Enza Maria; Gleeson, Joseph G.; Grattan-Smith, Padraic; Leventer, Richard; Janecke, Andreas; Van Coster, Rudy; Dias, Karin; Moco, Carla; Moreira, Ana; Chong, Ae Kim; Maegawa, Gustavo; Abdel-Salam, Ghada M H; Kamal Abd El Aleem, Alice; Zaki, Maha S.; Marti, Itxaso; Quijano-Roy, Susana; De Lonlay, Pascale; Verloes, Alain; Touraine, Renaud; Koenig, Michel; Lagier-Tourenne, Clotilde; Messer, Jean; Philippi, Heike; Tzeli, Sofia Kitsiou; Halldorsson, Saevar; Johannsdottir, Jonina; Ludvigsson, Peter; Magee, Alex; Lev, Dorit; Michelson, Marina; Ben-Zeev, Bruria; Fischetto, Rita; Gentile, Mattia; Battaglia, Silvia; Giordano, Lucio; Boccone, Loredana; Ruggieri, Martino; Bigoni, Stefania; Ferlini, Alessandra; Donati, Maria Alice; Procopio, Elena; Caridi, Gianluca; Faravelli, Francesca; Ghiggeri, Gianmarco; Briuglia, Silvana; Tortorella, Gaetano; D'Arrigo, Stefano; Pantaleoni, Chiara; Riva, Daria; Uziel, Graziella; Lavercla, Anna Maria; Permunian, Alberto; Bova, Stefania; Battini, Roberta; Cilio, Maria Roberta; Di Sabato, Marilù; Emma, Francesco; Leuzzi, Vincenzo; Parisi, Pasquale; Simonati, Alessandro; Al-Tawari, Asma A.; Bastaki, Laila; Aqeel, Ahmad; De Jong, Mirjam M.; Koul, Roshan; Rajab, Anna; Azam, Matloob; Barbot, Clara; Rodriguez, Berta; Pascual-Castroviejo, Ignacio; Comu, Sinan; Akcakus, Mustafa; Nicholl, David; Woods, C. Geoffrey; Bennett, Christopher; Hurst, Jane; Walsh, Christopher A.; Bernes, Saunder; Sanchez, Henry; Clark, Aldon E.; Donahue, Clement; Hahn, Jin; Sanger, Terence D.; Gallager, Tomas E.; Dobyns, William B.; Daugherty, Cynthia; Krishnamoorthy, Kalpathy S.; Sarco, Dean; McKanna, Trudy; Milisa, Joanne; Chung, Wendy K.; De Vivo, Darryl C.; Raynes, Hillary; Schubert, Romaine; Seward, Alison; Brooks, David G.; Goldstein, Amy; Caldwell, James; Finsecke, Eco; Maria, Bernard L.; Holden, Kenton; Cruse, Robert P.; Swoboda, Kathryn J.

In: American Journal of Human Genetics, Vol. 81, No. 1, 07.2007, p. 104-113.

Research output: Contribution to journalArticle

Brancati, F, Barrano, G, Silhavy, JL, Marsh, SE, Travaglini, L, Bielas, SL, Amorini, M, Zablocka, D, Kayserili, H, Al-Gazali, L, Bertini, E, Boltshauser, E, D'Hooghe, M, Fazzi, E, Fenerci, EY, Hennekam, RCM, Kiss, A, Lees, MM, Marco, E, Phadke, SR, Rigoli, L, Romano, S, Salpietro, CD, Sherr, EH, Signorini, S, Stromme, P, Stuart, B, Sztriha, L, Viskochil, DH, Yuksel, A, Dallapiccola, B, Valente, EM, Gleeson, JG, Grattan-Smith, P, Leventer, R, Janecke, A, Van Coster, R, Dias, K, Moco, C, Moreira, A, Chong, AK, Maegawa, G, Abdel-Salam, GMH, Kamal Abd El Aleem, A, Zaki, MS, Marti, I, Quijano-Roy, S, De Lonlay, P, Verloes, A, Touraine, R, Koenig, M, Lagier-Tourenne, C, Messer, J, Philippi, H, Tzeli, SK, Halldorsson, S, Johannsdottir, J, Ludvigsson, P, Magee, A, Lev, D, Michelson, M, Ben-Zeev, B, Fischetto, R, Gentile, M, Battaglia, S, Giordano, L, Boccone, L, Ruggieri, M, Bigoni, S, Ferlini, A, Donati, MA, Procopio, E, Caridi, G, Faravelli, F, Ghiggeri, G, Briuglia, S, Tortorella, G, D'Arrigo, S, Pantaleoni, C, Riva, D, Uziel, G, Lavercla, AM, Permunian, A, Bova, S, Battini, R, Cilio, MR, Di Sabato, M, Emma, F, Leuzzi, V, Parisi, P, Simonati, A, Al-Tawari, AA, Bastaki, L, Aqeel, A, De Jong, MM, Koul, R, Rajab, A, Azam, M, Barbot, C, Rodriguez, B, Pascual-Castroviejo, I, Comu, S, Akcakus, M, Nicholl, D, Woods, CG, Bennett, C, Hurst, J, Walsh, CA, Bernes, S, Sanchez, H, Clark, AE, Donahue, C, Hahn, J, Sanger, TD, Gallager, TE, Dobyns, WB, Daugherty, C, Krishnamoorthy, KS, Sarco, D, McKanna, T, Milisa, J, Chung, WK, De Vivo, DC, Raynes, H, Schubert, R, Seward, A, Brooks, DG, Goldstein, A, Caldwell, J, Finsecke, E, Maria, BL, Holden, K, Cruse, RP & Swoboda, KJ 2007, 'CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders', American Journal of Human Genetics, vol. 81, no. 1, pp. 104-113. https://doi.org/10.1086/519026
Brancati, Francesco ; Barrano, Giuseppe ; Silhavy, Jennifer L. ; Marsh, Sarah E. ; Travaglini, Lorena ; Bielas, Stephanie L. ; Amorini, Maria ; Zablocka, Dominika ; Kayserili, Hulya ; Al-Gazali, Lihadh ; Bertini, Enrico ; Boltshauser, Eugen ; D'Hooghe, Marc ; Fazzi, Elisa ; Fenerci, Elif Y. ; Hennekam, Raoul C M ; Kiss, Andrea ; Lees, Melissa M. ; Marco, Elysa ; Phadke, Shubha R. ; Rigoli, Luciana ; Romano, Stephane ; Salpietro, Carmelo D. ; Sherr, Elliott H. ; Signorini, Sabrina ; Stromme, Petter ; Stuart, Bernard ; Sztriha, Laszlo ; Viskochil, David H. ; Yuksel, Adnan ; Dallapiccola, Bruno ; Valente, Enza Maria ; Gleeson, Joseph G. ; Grattan-Smith, Padraic ; Leventer, Richard ; Janecke, Andreas ; Van Coster, Rudy ; Dias, Karin ; Moco, Carla ; Moreira, Ana ; Chong, Ae Kim ; Maegawa, Gustavo ; Abdel-Salam, Ghada M H ; Kamal Abd El Aleem, Alice ; Zaki, Maha S. ; Marti, Itxaso ; Quijano-Roy, Susana ; De Lonlay, Pascale ; Verloes, Alain ; Touraine, Renaud ; Koenig, Michel ; Lagier-Tourenne, Clotilde ; Messer, Jean ; Philippi, Heike ; Tzeli, Sofia Kitsiou ; Halldorsson, Saevar ; Johannsdottir, Jonina ; Ludvigsson, Peter ; Magee, Alex ; Lev, Dorit ; Michelson, Marina ; Ben-Zeev, Bruria ; Fischetto, Rita ; Gentile, Mattia ; Battaglia, Silvia ; Giordano, Lucio ; Boccone, Loredana ; Ruggieri, Martino ; Bigoni, Stefania ; Ferlini, Alessandra ; Donati, Maria Alice ; Procopio, Elena ; Caridi, Gianluca ; Faravelli, Francesca ; Ghiggeri, Gianmarco ; Briuglia, Silvana ; Tortorella, Gaetano ; D'Arrigo, Stefano ; Pantaleoni, Chiara ; Riva, Daria ; Uziel, Graziella ; Lavercla, Anna Maria ; Permunian, Alberto ; Bova, Stefania ; Battini, Roberta ; Cilio, Maria Roberta ; Di Sabato, Marilù ; Emma, Francesco ; Leuzzi, Vincenzo ; Parisi, Pasquale ; Simonati, Alessandro ; Al-Tawari, Asma A. ; Bastaki, Laila ; Aqeel, Ahmad ; De Jong, Mirjam M. ; Koul, Roshan ; Rajab, Anna ; Azam, Matloob ; Barbot, Clara ; Rodriguez, Berta ; Pascual-Castroviejo, Ignacio ; Comu, Sinan ; Akcakus, Mustafa ; Nicholl, David ; Woods, C. Geoffrey ; Bennett, Christopher ; Hurst, Jane ; Walsh, Christopher A. ; Bernes, Saunder ; Sanchez, Henry ; Clark, Aldon E. ; Donahue, Clement ; Hahn, Jin ; Sanger, Terence D. ; Gallager, Tomas E. ; Dobyns, William B. ; Daugherty, Cynthia ; Krishnamoorthy, Kalpathy S. ; Sarco, Dean ; McKanna, Trudy ; Milisa, Joanne ; Chung, Wendy K. ; De Vivo, Darryl C. ; Raynes, Hillary ; Schubert, Romaine ; Seward, Alison ; Brooks, David G. ; Goldstein, Amy ; Caldwell, James ; Finsecke, Eco ; Maria, Bernard L. ; Holden, Kenton ; Cruse, Robert P. ; Swoboda, Kathryn J. / CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. In: American Journal of Human Genetics. 2007 ; Vol. 81, No. 1. pp. 104-113.
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title = "CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders",
abstract = "Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MPS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-L{\"o}ken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.",
author = "Francesco Brancati and Giuseppe Barrano and Silhavy, {Jennifer L.} and Marsh, {Sarah E.} and Lorena Travaglini and Bielas, {Stephanie L.} and Maria Amorini and Dominika Zablocka and Hulya Kayserili and Lihadh Al-Gazali and Enrico Bertini and Eugen Boltshauser and Marc D'Hooghe and Elisa Fazzi and Fenerci, {Elif Y.} and Hennekam, {Raoul C M} and Andrea Kiss and Lees, {Melissa M.} and Elysa Marco and Phadke, {Shubha R.} and Luciana Rigoli and Stephane Romano and Salpietro, {Carmelo D.} and Sherr, {Elliott H.} and Sabrina Signorini and Petter Stromme and Bernard Stuart and Laszlo Sztriha and Viskochil, {David H.} and Adnan Yuksel and Bruno Dallapiccola and Valente, {Enza Maria} and Gleeson, {Joseph G.} and Padraic Grattan-Smith and Richard Leventer and Andreas Janecke and {Van Coster}, Rudy and Karin Dias and Carla Moco and Ana Moreira and Chong, {Ae Kim} and Gustavo Maegawa and Abdel-Salam, {Ghada M H} and {Kamal Abd El Aleem}, Alice and Zaki, {Maha S.} and Itxaso Marti and Susana Quijano-Roy and {De Lonlay}, Pascale and Alain Verloes and Renaud Touraine and Michel Koenig and Clotilde Lagier-Tourenne and Jean Messer and Heike Philippi and Tzeli, {Sofia Kitsiou} and Saevar Halldorsson and Jonina Johannsdottir and Peter Ludvigsson and Alex Magee and Dorit Lev and Marina Michelson and Bruria Ben-Zeev and Rita Fischetto and Mattia Gentile and Silvia Battaglia and Lucio Giordano and Loredana Boccone and Martino Ruggieri and Stefania Bigoni and Alessandra Ferlini and Donati, {Maria Alice} and Elena Procopio and Gianluca Caridi and Francesca Faravelli and Gianmarco Ghiggeri and Silvana Briuglia and Gaetano Tortorella and Stefano D'Arrigo and Chiara Pantaleoni and Daria Riva and Graziella Uziel and Lavercla, {Anna Maria} and Alberto Permunian and Stefania Bova and Roberta Battini and Cilio, {Maria Roberta} and {Di Sabato}, Maril{\`u} and Francesco Emma and Vincenzo Leuzzi and Pasquale Parisi and Alessandro Simonati and Al-Tawari, {Asma A.} and Laila Bastaki and Ahmad Aqeel and {De Jong}, {Mirjam M.} and Roshan Koul and Anna Rajab and Matloob Azam and Clara Barbot and Berta Rodriguez and Ignacio Pascual-Castroviejo and Sinan Comu and Mustafa Akcakus and David Nicholl and Woods, {C. Geoffrey} and Christopher Bennett and Jane Hurst and Walsh, {Christopher A.} and Saunder Bernes and Henry Sanchez and Clark, {Aldon E.} and Clement Donahue and Jin Hahn and Sanger, {Terence D.} and Gallager, {Tomas E.} and Dobyns, {William B.} and Cynthia Daugherty and Krishnamoorthy, {Kalpathy S.} and Dean Sarco and Trudy McKanna and Joanne Milisa and Chung, {Wendy K.} and {De Vivo}, {Darryl C.} and Hillary Raynes and Romaine Schubert and Alison Seward and Brooks, {David G.} and Amy Goldstein and James Caldwell and Eco Finsecke and Maria, {Bernard L.} and Kenton Holden and Cruse, {Robert P.} and Swoboda, {Kathryn J.}",
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T1 - CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders

AU - Brancati, Francesco

AU - Barrano, Giuseppe

AU - Silhavy, Jennifer L.

AU - Marsh, Sarah E.

AU - Travaglini, Lorena

AU - Bielas, Stephanie L.

AU - Amorini, Maria

AU - Zablocka, Dominika

AU - Kayserili, Hulya

AU - Al-Gazali, Lihadh

AU - Bertini, Enrico

AU - Boltshauser, Eugen

AU - D'Hooghe, Marc

AU - Fazzi, Elisa

AU - Fenerci, Elif Y.

AU - Hennekam, Raoul C M

AU - Kiss, Andrea

AU - Lees, Melissa M.

AU - Marco, Elysa

AU - Phadke, Shubha R.

AU - Rigoli, Luciana

AU - Romano, Stephane

AU - Salpietro, Carmelo D.

AU - Sherr, Elliott H.

AU - Signorini, Sabrina

AU - Stromme, Petter

AU - Stuart, Bernard

AU - Sztriha, Laszlo

AU - Viskochil, David H.

AU - Yuksel, Adnan

AU - Dallapiccola, Bruno

AU - Valente, Enza Maria

AU - Gleeson, Joseph G.

AU - Grattan-Smith, Padraic

AU - Leventer, Richard

AU - Janecke, Andreas

AU - Van Coster, Rudy

AU - Dias, Karin

AU - Moco, Carla

AU - Moreira, Ana

AU - Chong, Ae Kim

AU - Maegawa, Gustavo

AU - Abdel-Salam, Ghada M H

AU - Kamal Abd El Aleem, Alice

AU - Zaki, Maha S.

AU - Marti, Itxaso

AU - Quijano-Roy, Susana

AU - De Lonlay, Pascale

AU - Verloes, Alain

AU - Touraine, Renaud

AU - Koenig, Michel

AU - Lagier-Tourenne, Clotilde

AU - Messer, Jean

AU - Philippi, Heike

AU - Tzeli, Sofia Kitsiou

AU - Halldorsson, Saevar

AU - Johannsdottir, Jonina

AU - Ludvigsson, Peter

AU - Magee, Alex

AU - Lev, Dorit

AU - Michelson, Marina

AU - Ben-Zeev, Bruria

AU - Fischetto, Rita

AU - Gentile, Mattia

AU - Battaglia, Silvia

AU - Giordano, Lucio

AU - Boccone, Loredana

AU - Ruggieri, Martino

AU - Bigoni, Stefania

AU - Ferlini, Alessandra

AU - Donati, Maria Alice

AU - Procopio, Elena

AU - Caridi, Gianluca

AU - Faravelli, Francesca

AU - Ghiggeri, Gianmarco

AU - Briuglia, Silvana

AU - Tortorella, Gaetano

AU - D'Arrigo, Stefano

AU - Pantaleoni, Chiara

AU - Riva, Daria

AU - Uziel, Graziella

AU - Lavercla, Anna Maria

AU - Permunian, Alberto

AU - Bova, Stefania

AU - Battini, Roberta

AU - Cilio, Maria Roberta

AU - Di Sabato, Marilù

AU - Emma, Francesco

AU - Leuzzi, Vincenzo

AU - Parisi, Pasquale

AU - Simonati, Alessandro

AU - Al-Tawari, Asma A.

AU - Bastaki, Laila

AU - Aqeel, Ahmad

AU - De Jong, Mirjam M.

AU - Koul, Roshan

AU - Rajab, Anna

AU - Azam, Matloob

AU - Barbot, Clara

AU - Rodriguez, Berta

AU - Pascual-Castroviejo, Ignacio

AU - Comu, Sinan

AU - Akcakus, Mustafa

AU - Nicholl, David

AU - Woods, C. Geoffrey

AU - Bennett, Christopher

AU - Hurst, Jane

AU - Walsh, Christopher A.

AU - Bernes, Saunder

AU - Sanchez, Henry

AU - Clark, Aldon E.

AU - Donahue, Clement

AU - Hahn, Jin

AU - Sanger, Terence D.

AU - Gallager, Tomas E.

AU - Dobyns, William B.

AU - Daugherty, Cynthia

AU - Krishnamoorthy, Kalpathy S.

AU - Sarco, Dean

AU - McKanna, Trudy

AU - Milisa, Joanne

AU - Chung, Wendy K.

AU - De Vivo, Darryl C.

AU - Raynes, Hillary

AU - Schubert, Romaine

AU - Seward, Alison

AU - Brooks, David G.

AU - Goldstein, Amy

AU - Caldwell, James

AU - Finsecke, Eco

AU - Maria, Bernard L.

AU - Holden, Kenton

AU - Cruse, Robert P.

AU - Swoboda, Kathryn J.

PY - 2007/7

Y1 - 2007/7

N2 - Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MPS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Löken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.

AB - Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MPS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Löken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.

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U2 - 10.1086/519026

DO - 10.1086/519026

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SP - 104

EP - 113

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

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