Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients

Futoshi Sekiguchi, Yoshinori Tsurusaki, Nobuhiko Okamoto, Keng Wee Teik, Seiji Mizuno, Hiroshi Suzumura, Bertrand Isidor, Winnie Peitee Ong, Muzhirah Haniffa, Susan M. White, Mari Matsuo, Kayoko Saito, Shubha Phadke, Tomoki Kosho, Patrick Yap, Manisha Goyal, Lorne A. Clarke, Rani Sachdev, George McGillivray, Richard J. LeventerChirag Patel, Takanori Yamagata, Hitoshi Osaka, Yoshiya Hisaeda, Hirofumi Ohashi, Kenji Shimizu, Keisuke Nagasaki, Junpei Hamada, Sumito Dateki, Takashi Sato, Yasutsugu Chinen, Tomonari Awaya, Takeo Kato, Kougoro Iwanaga, Masahiko Kawai, Takashi Matsuoka, Yoshikazu Shimoji, Tiong Yang Tan, Seema Kapoor, Nerine Gregersen, Massimiliano Rossi, Mathieu Marie-Laure, Lesley McGregor, Kimihiko Oishi, Lakshmi Mehta, Greta Gillies, Paul J. Lockhart, Kate Pope, Anju Shukla, Katta Mohan Girisha, Ghada M.H. Abdel-Salam, David Mowat, David Coman, Ok Hwa Kim, Marie Pierre Cordier, Kate Gibson, Jeff Milunsky, Jan Liebelt, Helen Cox, Salima El Chehadeh, Annick Toutain, Ken Saida, Hiromi Aoi, Gaku Minase, Naomi Tsuchida, Kazuhiro Iwama, Yuri Uchiyama, Toshifumi Suzuki, Kohei Hamanaka, Yoshiteru Azuma, Atsushi Fujita, Eri Imagawa, Eriko Koshimizu, Atsushi Takata, Satomi Mitsuhashi, Satoko Miyatake, Takeshi Mizuguchi, Noriko Miyake, Naomichi Matsumoto

Research output: Contribution to journalArticle

Abstract

Coffin–Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.

Original languageEnglish
Pages (from-to)1173-1186
Number of pages14
JournalJournal of Human Genetics
Volume64
Issue number12
DOIs
Publication statusPublished - 01-12-2019

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Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Chromatin Assembly and Disassembly
Nails
Intellectual Disability
Nucleotides
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Sekiguchi, F., Tsurusaki, Y., Okamoto, N., Teik, K. W., Mizuno, S., Suzumura, H., ... Matsumoto, N. (2019). Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients. Journal of Human Genetics, 64(12), 1173-1186. https://doi.org/10.1038/s10038-019-0667-4
Sekiguchi, Futoshi ; Tsurusaki, Yoshinori ; Okamoto, Nobuhiko ; Teik, Keng Wee ; Mizuno, Seiji ; Suzumura, Hiroshi ; Isidor, Bertrand ; Ong, Winnie Peitee ; Haniffa, Muzhirah ; White, Susan M. ; Matsuo, Mari ; Saito, Kayoko ; Phadke, Shubha ; Kosho, Tomoki ; Yap, Patrick ; Goyal, Manisha ; Clarke, Lorne A. ; Sachdev, Rani ; McGillivray, George ; Leventer, Richard J. ; Patel, Chirag ; Yamagata, Takanori ; Osaka, Hitoshi ; Hisaeda, Yoshiya ; Ohashi, Hirofumi ; Shimizu, Kenji ; Nagasaki, Keisuke ; Hamada, Junpei ; Dateki, Sumito ; Sato, Takashi ; Chinen, Yasutsugu ; Awaya, Tomonari ; Kato, Takeo ; Iwanaga, Kougoro ; Kawai, Masahiko ; Matsuoka, Takashi ; Shimoji, Yoshikazu ; Tan, Tiong Yang ; Kapoor, Seema ; Gregersen, Nerine ; Rossi, Massimiliano ; Marie-Laure, Mathieu ; McGregor, Lesley ; Oishi, Kimihiko ; Mehta, Lakshmi ; Gillies, Greta ; Lockhart, Paul J. ; Pope, Kate ; Shukla, Anju ; Girisha, Katta Mohan ; Abdel-Salam, Ghada M.H. ; Mowat, David ; Coman, David ; Kim, Ok Hwa ; Cordier, Marie Pierre ; Gibson, Kate ; Milunsky, Jeff ; Liebelt, Jan ; Cox, Helen ; El Chehadeh, Salima ; Toutain, Annick ; Saida, Ken ; Aoi, Hiromi ; Minase, Gaku ; Tsuchida, Naomi ; Iwama, Kazuhiro ; Uchiyama, Yuri ; Suzuki, Toshifumi ; Hamanaka, Kohei ; Azuma, Yoshiteru ; Fujita, Atsushi ; Imagawa, Eri ; Koshimizu, Eriko ; Takata, Atsushi ; Mitsuhashi, Satomi ; Miyatake, Satoko ; Mizuguchi, Takeshi ; Miyake, Noriko ; Matsumoto, Naomichi. / Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients. In: Journal of Human Genetics. 2019 ; Vol. 64, No. 12. pp. 1173-1186.
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abstract = "Coffin–Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.",
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Sekiguchi, F, Tsurusaki, Y, Okamoto, N, Teik, KW, Mizuno, S, Suzumura, H, Isidor, B, Ong, WP, Haniffa, M, White, SM, Matsuo, M, Saito, K, Phadke, S, Kosho, T, Yap, P, Goyal, M, Clarke, LA, Sachdev, R, McGillivray, G, Leventer, RJ, Patel, C, Yamagata, T, Osaka, H, Hisaeda, Y, Ohashi, H, Shimizu, K, Nagasaki, K, Hamada, J, Dateki, S, Sato, T, Chinen, Y, Awaya, T, Kato, T, Iwanaga, K, Kawai, M, Matsuoka, T, Shimoji, Y, Tan, TY, Kapoor, S, Gregersen, N, Rossi, M, Marie-Laure, M, McGregor, L, Oishi, K, Mehta, L, Gillies, G, Lockhart, PJ, Pope, K, Shukla, A, Girisha, KM, Abdel-Salam, GMH, Mowat, D, Coman, D, Kim, OH, Cordier, MP, Gibson, K, Milunsky, J, Liebelt, J, Cox, H, El Chehadeh, S, Toutain, A, Saida, K, Aoi, H, Minase, G, Tsuchida, N, Iwama, K, Uchiyama, Y, Suzuki, T, Hamanaka, K, Azuma, Y, Fujita, A, Imagawa, E, Koshimizu, E, Takata, A, Mitsuhashi, S, Miyatake, S, Mizuguchi, T, Miyake, N & Matsumoto, N 2019, 'Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients', Journal of Human Genetics, vol. 64, no. 12, pp. 1173-1186. https://doi.org/10.1038/s10038-019-0667-4

Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients. / Sekiguchi, Futoshi; Tsurusaki, Yoshinori; Okamoto, Nobuhiko; Teik, Keng Wee; Mizuno, Seiji; Suzumura, Hiroshi; Isidor, Bertrand; Ong, Winnie Peitee; Haniffa, Muzhirah; White, Susan M.; Matsuo, Mari; Saito, Kayoko; Phadke, Shubha; Kosho, Tomoki; Yap, Patrick; Goyal, Manisha; Clarke, Lorne A.; Sachdev, Rani; McGillivray, George; Leventer, Richard J.; Patel, Chirag; Yamagata, Takanori; Osaka, Hitoshi; Hisaeda, Yoshiya; Ohashi, Hirofumi; Shimizu, Kenji; Nagasaki, Keisuke; Hamada, Junpei; Dateki, Sumito; Sato, Takashi; Chinen, Yasutsugu; Awaya, Tomonari; Kato, Takeo; Iwanaga, Kougoro; Kawai, Masahiko; Matsuoka, Takashi; Shimoji, Yoshikazu; Tan, Tiong Yang; Kapoor, Seema; Gregersen, Nerine; Rossi, Massimiliano; Marie-Laure, Mathieu; McGregor, Lesley; Oishi, Kimihiko; Mehta, Lakshmi; Gillies, Greta; Lockhart, Paul J.; Pope, Kate; Shukla, Anju; Girisha, Katta Mohan; Abdel-Salam, Ghada M.H.; Mowat, David; Coman, David; Kim, Ok Hwa; Cordier, Marie Pierre; Gibson, Kate; Milunsky, Jeff; Liebelt, Jan; Cox, Helen; El Chehadeh, Salima; Toutain, Annick; Saida, Ken; Aoi, Hiromi; Minase, Gaku; Tsuchida, Naomi; Iwama, Kazuhiro; Uchiyama, Yuri; Suzuki, Toshifumi; Hamanaka, Kohei; Azuma, Yoshiteru; Fujita, Atsushi; Imagawa, Eri; Koshimizu, Eriko; Takata, Atsushi; Mitsuhashi, Satomi; Miyatake, Satoko; Mizuguchi, Takeshi; Miyake, Noriko; Matsumoto, Naomichi.

In: Journal of Human Genetics, Vol. 64, No. 12, 01.12.2019, p. 1173-1186.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients

AU - Sekiguchi, Futoshi

AU - Tsurusaki, Yoshinori

AU - Okamoto, Nobuhiko

AU - Teik, Keng Wee

AU - Mizuno, Seiji

AU - Suzumura, Hiroshi

AU - Isidor, Bertrand

AU - Ong, Winnie Peitee

AU - Haniffa, Muzhirah

AU - White, Susan M.

AU - Matsuo, Mari

AU - Saito, Kayoko

AU - Phadke, Shubha

AU - Kosho, Tomoki

AU - Yap, Patrick

AU - Goyal, Manisha

AU - Clarke, Lorne A.

AU - Sachdev, Rani

AU - McGillivray, George

AU - Leventer, Richard J.

AU - Patel, Chirag

AU - Yamagata, Takanori

AU - Osaka, Hitoshi

AU - Hisaeda, Yoshiya

AU - Ohashi, Hirofumi

AU - Shimizu, Kenji

AU - Nagasaki, Keisuke

AU - Hamada, Junpei

AU - Dateki, Sumito

AU - Sato, Takashi

AU - Chinen, Yasutsugu

AU - Awaya, Tomonari

AU - Kato, Takeo

AU - Iwanaga, Kougoro

AU - Kawai, Masahiko

AU - Matsuoka, Takashi

AU - Shimoji, Yoshikazu

AU - Tan, Tiong Yang

AU - Kapoor, Seema

AU - Gregersen, Nerine

AU - Rossi, Massimiliano

AU - Marie-Laure, Mathieu

AU - McGregor, Lesley

AU - Oishi, Kimihiko

AU - Mehta, Lakshmi

AU - Gillies, Greta

AU - Lockhart, Paul J.

AU - Pope, Kate

AU - Shukla, Anju

AU - Girisha, Katta Mohan

AU - Abdel-Salam, Ghada M.H.

AU - Mowat, David

AU - Coman, David

AU - Kim, Ok Hwa

AU - Cordier, Marie Pierre

AU - Gibson, Kate

AU - Milunsky, Jeff

AU - Liebelt, Jan

AU - Cox, Helen

AU - El Chehadeh, Salima

AU - Toutain, Annick

AU - Saida, Ken

AU - Aoi, Hiromi

AU - Minase, Gaku

AU - Tsuchida, Naomi

AU - Iwama, Kazuhiro

AU - Uchiyama, Yuri

AU - Suzuki, Toshifumi

AU - Hamanaka, Kohei

AU - Azuma, Yoshiteru

AU - Fujita, Atsushi

AU - Imagawa, Eri

AU - Koshimizu, Eriko

AU - Takata, Atsushi

AU - Mitsuhashi, Satomi

AU - Miyatake, Satoko

AU - Mizuguchi, Takeshi

AU - Miyake, Noriko

AU - Matsumoto, Naomichi

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Coffin–Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.

AB - Coffin–Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.

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Sekiguchi F, Tsurusaki Y, Okamoto N, Teik KW, Mizuno S, Suzumura H et al. Genetic abnormalities in a large cohort of Coffin–Siris syndrome patients. Journal of Human Genetics. 2019 Dec 1;64(12):1173-1186. https://doi.org/10.1038/s10038-019-0667-4