Shino Shimada1, Keiko Shimojima2, Nobuhiko Okamoto3, Noriko Sangu4, Kyoko Hirasawa5, Mari Matsuo6, Mayo Ikeuchi7, Shuichi Shimakawa8, Kenji Shimizu9, Seiji Mizuno10, Masaya Kubota11, Masao Adachi12, Yoshiaki Saito13, Kiyotaka Tomiwa14, Kazuhiro Haginoya15, Hironao Numabe16, Yuko Kako17, Ai Hayashi18, Haruko Sakamoto19, Yoko Hiraki20, Koichi Minami21, Kiyoshi Takemoto22, Kyoko Watanabe23, Kiyokuni Miura24, Tomohiro Chiyonobu25, Tomohiro Kumada26, Katsumi Imai27, Yoshihiro Maegaki28, Satoru Nagata5, Kenjiro Kosaki29, Tatsuro Izumi7, Toshiro Nagai30, Toshiyuki Yamamoto31. 1. Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan. 2. Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. 3. Department of Medical Genetics, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan. 4. Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan; Department of Oral and Maxillofacial Surgery, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan. 5. Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan. 6. Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan. 7. Department of Pediatrics and Child Neurology, Oita University Faculty of Medicine, Oita, Japan. 8. Department of Pediatrics, Osaka Medical College, Takatsuki, Japan. 9. Division of Medical Genetics, Saitama Children's Medical Center, Saitama, Japan. 10. Department of Pediatrics, Central Hospital, Aichi Human Service Center, Kasugai, Japan. 11. Division of Neurology, National Center for Child Health and Development, Tokyo, Japan. 12. Department of Pediatrics, Kakogawa Hospital Organization, Kakogawa West-City Hospital, Kakogawa, Japan. 13. Department of Child Neurology, National Center of Neurology and Psychiatry, Tokyo, Japan. 14. Department of Pediatrics, Medical Center for Children, Osaka City General Hospital, Osaka, Japan. 15. Department of Pediatric Neurology, Takuto Rehabilitation Center for Children, Sendai, Japan. 16. Department of Genetic Counseling, Graduate School of Humanities and Sciences, Ochanomizu University, Tokyo, Japan. 17. Department of Pediatrics, Showa University School of Medicine, Tokyo, Japan. 18. Department of Neonatology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan. 19. Department of Pediatrics, Osaka Red Cross Hospital, Osaka, Japan. 20. Hiroshima Municipal Center for Child Health and Development, Hiroshima, Japan. 21. Department of Pediatrics, Wakayama Medical University, Wakayama, Japan. 22. Osaka Developmental Rehabilitation Center, Osaka, Japan. 23. Department of Pediatrics, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan. 24. Developmental Disability Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. 25. Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan. 26. Department of Pediatrics, Shiga Medical Center for Children, Moriyama, Japan. 27. National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan. 28. Division of Child Neurology, Tottori University School of Medicine, Yonago, Japan. 29. Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan. 30. Department of Pediatrics, Dokkyo Medical University Koshigaya Hospital, Saitama, Japan. 31. Tokyo Women's Medical University Institute for Integrated Medical Sciences, Tokyo, Japan. Electronic address: yamamoto.toshiyuki@twmu.ac.jp.
Abstract
OBJECTIVE: Monosomy 1p36 syndrome is the most commonly observed subtelomeric deletion syndrome. Patients with this syndrome typically have common clinical features, such as intellectual disability, epilepsy, and characteristic craniofacial features. METHOD: In cooperation with academic societies, we analyzed the genomic copy number aberrations using chromosomal microarray testing. Finally, the genotype-phenotype correlation among them was examined. RESULTS: We obtained clinical information of 86 patients who had been diagnosed with chromosomal deletions in the 1p36 region. Among them, blood samples were obtained from 50 patients (15 males and 35 females). The precise deletion regions were successfully genotyped. There were variable deletion patterns: pure terminal deletions in 38 patients (76%), including three cases of mosaicism; unbalanced translocations in seven (14%); and interstitial deletions in five (10%). Craniofacial/skeletal features, neurodevelopmental impairments, and cardiac anomalies were commonly observed in patients, with correlation to deletion sizes. CONCLUSION: The genotype-phenotype correlation analysis narrowed the region responsible for distinctive craniofacial features and intellectual disability into 1.8-2.1 and 1.8-2.2 Mb region, respectively. Patients with deletions larger than 6.2 Mb showed no ambulation, indicating that severe neurodevelopmental prognosis may be modified by haploinsufficiencies of KCNAB2 and CHD5, located at 6.2 Mb away from the telomere. Although the genotype-phenotype correlation for the cardiac abnormalities is unclear, PRDM16, PRKCZ, and RERE may be related to this complication. Our study also revealed that female patients who acquired ambulatory ability were likely to be at risk for obesity.
OBJECTIVE: Monosomy 1p36 syndrome is the most commonly observed subtelomeric deletion syndrome. Patients with this syndrome typically have common clinical features, such as intellectual disability, epilepsy, and characteristic craniofacial features. METHOD: In cooperation with academic societies, we analyzed the genomic copy number aberrations using chromosomal microarray testing. Finally, the genotype-phenotype correlation among them was examined. RESULTS: We obtained clinical information of 86 patients who had been diagnosed with chromosomal deletions in the 1p36 region. Among them, blood samples were obtained from 50 patients (15 males and 35 females). The precise deletion regions were successfully genotyped. There were variable deletion patterns: pure terminal deletions in 38 patients (76%), including three cases of mosaicism; unbalanced translocations in seven (14%); and interstitial deletions in five (10%). Craniofacial/skeletal features, neurodevelopmental impairments, and cardiac anomalies were commonly observed in patients, with correlation to deletion sizes. CONCLUSION: The genotype-phenotype correlation analysis narrowed the region responsible for distinctive craniofacial features and intellectual disability into 1.8-2.1 and 1.8-2.2 Mb region, respectively. Patients with deletions larger than 6.2 Mb showed no ambulation, indicating that severe neurodevelopmental prognosis may be modified by haploinsufficiencies of KCNAB2 and CHD5, located at 6.2 Mb away from the telomere. Although the genotype-phenotype correlation for the cardiac abnormalities is unclear, PRDM16, PRKCZ, and RERE may be related to this complication. Our study also revealed that female patients who acquired ambulatory ability were likely to be at risk for obesity.
Authors: Brieana Fregeau; Bum Jun Kim; Andrés Hernández-García; Valerie K Jordan; Megan T Cho; Rhonda E Schnur; Kristin G Monaghan; Jane Juusola; Jill A Rosenfeld; Elizabeth Bhoj; Elaine H Zackai; Stephanie Sacharow; Kristin Barañano; Daniëlle G M Bosch; Bert B A de Vries; Kristin Lindstrom; Audrey Schroeder; Philip James; Peggy Kulch; Seema R Lalani; Mieke M van Haelst; Koen L I van Gassen; Ellen van Binsbergen; A James Barkovich; Daryl A Scott; Elliott H Sherr Journal: Am J Hum Genet Date: 2016-04-14 Impact factor: 11.025
Authors: Francesca Clementina Radio; Kaifang Pang; Andrea Ciolfi; Michael A Levy; Andrés Hernández-García; Lucia Pedace; Francesca Pantaleoni; Zhandong Liu; Elke de Boer; Adam Jackson; Alessandro Bruselles; Haley McConkey; Emilia Stellacci; Stefania Lo Cicero; Marialetizia Motta; Rosalba Carrozzo; Maria Lisa Dentici; Kirsty McWalter; Megha Desai; Kristin G Monaghan; Aida Telegrafi; Christophe Philippe; Antonio Vitobello; Margaret Au; Katheryn Grand; Pedro A Sanchez-Lara; Joanne Baez; Kristin Lindstrom; Peggy Kulch; Jessica Sebastian; Suneeta Madan-Khetarpal; Chelsea Roadhouse; Jennifer J MacKenzie; Berrin Monteleone; Carol J Saunders; July K Jean Cuevas; Laura Cross; Dihong Zhou; Taila Hartley; Sarah L Sawyer; Fabíola Paoli Monteiro; Tania Vertemati Secches; Fernando Kok; Laura E Schultz-Rogers; Erica L Macke; Eva Morava; Eric W Klee; Jennifer Kemppainen; Maria Iascone; Angelo Selicorni; Romano Tenconi; David J Amor; Lynn Pais; Lyndon Gallacher; Peter D Turnpenny; Karen Stals; Sian Ellard; Sara Cabet; Gaetan Lesca; Joset Pascal; Katharina Steindl; Sarit Ravid; Karin Weiss; Alison M R Castle; Melissa T Carter; Louisa Kalsner; Bert B A de Vries; Bregje W van Bon; Marijke R Wevers; Rolph Pfundt; Alexander P A Stegmann; Bronwyn Kerr; Helen M Kingston; Kate E Chandler; Willow Sheehan; Abdallah F Elias; Deepali N Shinde; Meghan C Towne; Nathaniel H Robin; Dana Goodloe; Adeline Vanderver; Omar Sherbini; Krista Bluske; R Tanner Hagelstrom; Caterina Zanus; Flavio Faletra; Luciana Musante; Evangeline C Kurtz-Nelson; Rachel K Earl; Britt-Marie Anderlid; Gilles Morin; Marjon van Slegtenhorst; Karin E M Diderich; Alice S Brooks; Joost Gribnau; Ruben G Boers; Teresa Robert Finestra; Lauren B Carter; Anita Rauch; Paolo Gasparini; Kym M Boycott; Tahsin Stefan Barakat; John M Graham; Laurence Faivre; Siddharth Banka; Tianyun Wang; Evan E Eichler; Manuela Priolo; Bruno Dallapiccola; Lisenka E L M Vissers; Bekim Sadikovic; Daryl A Scott; Jimmy Lloyd Holder; Marco Tartaglia Journal: Am J Hum Genet Date: 2021-02-16 Impact factor: 11.025
Authors: Ilaria Parenti; Daphné Lehalle; Christel Depienne; Cyril Mignot; Caroline Nava; Erin Torti; Elsa Leitão; Richard Person; Takeshi Mizuguchi; Naomichi Matsumoto; Mitsuhiro Kato; Kazuyuki Nakamura; Stella A de Man; Heidi Cope; Vandana Shashi; Jennifer Friedman; Pascal Joset; Katharina Steindl; Anita Rauch; Irena Muffels; Peter M van Hasselt; Florence Petit; Thomas Smol; Gwenaël Le Guyader; Frédéric Bilan; Arthur Sorlin; Antonio Vitobello; Christophe Philippe; Ingrid M B H van de Laar; Marjon A van Slegtenhorst; Philippe M Campeau; Ping Yee Billie Au; Mitsuko Nakashima; Hirotomo Saitsu; Tatsuya Yamamoto; Yumiko Nomura; Raymond J Louie; Michael J Lyons; Amy Dobson; Astrid S Plomp; M Mahdi Motazacker; Frank J Kaiser; Andrew T Timberlake; Sabine A Fuchs Journal: Hum Genet Date: 2021-05-04 Impact factor: 4.132
Authors: Rebecca V Steenaard; Symen Ligthart; Lisette Stolk; Marjolein J Peters; Joyce B van Meurs; Andre G Uitterlinden; Albert Hofman; Oscar H Franco; Abbas Dehghan Journal: Clin Epigenetics Date: 2015-05-14 Impact factor: 6.551