Gali Heimer1, Danit Oz-Levi2, Eran Eyal3, Shimon Edvardson4, Andreea Nissenkorn5, Elizabeth K Ruzzo6, Amir Szeinberg7, Channa Maayan8, Meir Mai-Zahav9, Ori Efrati10, Elon Pras11, Haike Reznik-Wolf12, Doron Lancet2, David B Goldstein13, Yair Anikster14, Stavit A Shalev15, Orly Elpeleg4, Bruria Ben Zeev16. 1. Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel; The Pinchas Borenstein Talpiot Medical Leadership Program, The Chaim Sheba Med. Ctr., Israel. Electronic address: galih.md@gmail.com. 2. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel. 3. Cancer Research Center, Pediatric Hemato/Oncology Unit, Edmond and Lily Safra Children's, Hospital, The Chaim Sheba Med. Ctr., Israel. 4. Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University, Med. Ctr., Jerusalem, Israel. 5. Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel; The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel. 6. Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, USA. 7. Pediatric Sleep clinic, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel. 8. Familial Dysautonomia Centre, Pediatric Department, Hadassah Hospital, Hebrew University Hadassah, Medical School, Jerusalem, Israel. 9. Pulmonary Institute, Schneider Children's Med. Ctr., Sackler Faculty of Medicine, Tel Aviv University, Israel. 10. The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel; Pediatric Pulmonary Unit, The Edmond and Lily Safra Children's Hospital, Sheba Med. Ctr., Israel. 11. The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel; Danek Gertner Institute of Human Genetics, Sheba Med. Ctr., Ramat Gan, Israel. 12. Danek Gertner Institute of Human Genetics, Sheba Med. Ctr., Ramat Gan, Israel. 13. Institute for Genomic Medicine, Columbia University Medical School, Columbia University Med. Ctr., New York, NY 10032, USA. 14. The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel; Metabolic Disease Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel. 15. Genetic Institute, Ha'Emek Med. Ctr., Afula 18101, Israel; Rappaport Faculty of Medicine, Technion, Israel. 16. Pediatric Neurology Unit, Edmond and Lily Safra Children's Hospital, The Chaim Sheba Med. Ctr., Israel; The Sackler School of Medicine, Tel Aviv University, 69978, Tel Aviv, Israel. Electronic address: bruria.benzeev@sheba.health.gov.il.
Abstract
BACKGROUND: TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49). RESULTS: We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events. CONCLUSION: We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin.
BACKGROUND:TECPR2 was first described as a disease causing gene when the c.3416delT frameshift mutation was found in five Jewish Bukharian patients with similar features. It was suggested to constitute a new subtype of complex hereditary spastic paraparesis (SPG49). RESULTS: We report here 3 additional patients from unrelated non-Bukharian families, harboring two novel mutations (c.1319delT, c.C566T) in this gene. Accumulating clinical data clarifies that in addition to intellectual disability and evolving spasticity the main disabling feature of this unique disorder is autonomic-sensory neuropathy accompanied by chronic respiratory disease and paroxysmal autonomic events. CONCLUSION: We suggest that the disease should therefore be classified as a new subtype of hereditary sensory-autonomic neuropathy. The discovery of additional mutations in non-Bukharian patients implies that this disease might be more common than previously appreciated and should therefore be considered in undiagnosed cases of intellectual disability with autonomic features and respiratory symptoms regardless of demographic origin.
Authors: Andrey A Yurchenko; Tatiana E Deniskova; Nikolay S Yudin; Arsen V Dotsev; Timur N Khamiruev; Marina I Selionova; Sergey V Egorov; Henry Reyer; Klaus Wimmers; Gottfried Brem; Natalia A Zinovieva; Denis M Larkin Journal: BMC Genomics Date: 2019-05-08 Impact factor: 3.969
Authors: Daniel J Klionsky; Giulia Petroni; Ravi K Amaravadi; Eric H Baehrecke; Andrea Ballabio; Patricia Boya; José Manuel Bravo-San Pedro; Ken Cadwell; Francesco Cecconi; Augustine M K Choi; Mary E Choi; Charleen T Chu; Patrice Codogno; Maria Isabel Colombo; Ana Maria Cuervo; Vojo Deretic; Ivan Dikic; Zvulun Elazar; Eeva-Liisa Eskelinen; Gian Maria Fimia; David A Gewirtz; Douglas R Green; Malene Hansen; Marja Jäättelä; Terje Johansen; Gábor Juhász; Vassiliki Karantza; Claudine Kraft; Guido Kroemer; Nicholas T Ktistakis; Sharad Kumar; Carlos Lopez-Otin; Kay F Macleod; Frank Madeo; Jennifer Martinez; Alicia Meléndez; Noboru Mizushima; Christian Münz; Josef M Penninger; Rushika M Perera; Mauro Piacentini; Fulvio Reggiori; David C Rubinsztein; Kevin M Ryan; Junichi Sadoshima; Laura Santambrogio; Luca Scorrano; Hans-Uwe Simon; Anna Katharina Simon; Anne Simonsen; Alexandra Stolz; Nektarios Tavernarakis; Sharon A Tooze; Tamotsu Yoshimori; Junying Yuan; Zhenyu Yue; Qing Zhong; Lorenzo Galluzzi; Federico Pietrocola Journal: EMBO J Date: 2021-08-30 Impact factor: 14.012
Authors: Annette Lischka; Petra Lassuthova; Arman Çakar; Christopher J Record; Jonas Van Lent; Jonathan Baets; Maike F Dohrn; Jan Senderek; Angelika Lampert; David L Bennett; John N Wood; Vincent Timmerman; Thorsten Hornemann; Michaela Auer-Grumbach; Yesim Parman; Christian A Hübner; Miriam Elbracht; Katja Eggermann; C Geoffrey Woods; James J Cox; Mary M Reilly; Ingo Kurth Journal: Nat Rev Dis Primers Date: 2022-06-16 Impact factor: 65.038