Expanding the Mutational Spectrum of CRLF1 in Crisponi/CISS1 Syndrome |
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| Authors: | Roberta Piras Francesca Chiappe Ilaria La Torraca Insa Buers Gianluca Usala Andrea Angius Mustafa Ali Akin Lina Basel‐Vanagaite Francesco Benedicenti Elisabetta Chiodin Osama El Assy Michal Feingold‐Zadok Javier Guibert Benjamin Kamien Çiğdem Seher Kasapkara Esra Kılıç Koray Boduroğlu Selim Kurtoglu Adnan Y Manzur Eray Esra Onal Enrica Paderi Carmen Herrero Roche Leyla Tümer Sezin Unal Gülen Eda Utine Giovanni Zanda Andreas Zankl Giuseppe Zampino Giangiorgio Crisponi Laura Crisponi Frank Rutsch |
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| Institution: | 1. Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Cagliari, Italy;2. Department of Public Health and Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy;3. Istituto di Pediatria, Policlinico “A. Gemelli”, Università Cattolica del S. Cuore, Rome, Italy;4. Department of General Pediatrics, Münster University Children's Hospital, Münster, Germany;5. CRS4 Center for Advanced Studies, Research and Development in Sardinia, Laboratorio di Bioinformatica, Parco tecnologico della Sardegna, Pula, Italy;6. Department of Pediatrics, Medical Faculty, Erciyes University, Kayseri, Turkey;7. Pediatric Genetics, Schneider Children's Medical Center of Israel, and Raphael Recanati Genetic Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel;8. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;9. Felsenstein Medical Research Center, Tel Aviv University, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel;10. Genetic Counseling Service, Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy;11. Neonatal Intensive Care Unit, Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy;12. Pediatric Department‐NICU, Al‐Hada Military Hospital, Taif, Saudi Arabia;13. Servicio de Pediatría, Complejo Hospitalario de Navarra, Pamplona, Spain;14. Queensland Health Pathology, Royal Brisbane Hospital, Herston, Australia;15. Gazi University Hospital, Pediatric Metabolism and Nutrition, Ankara, Turkey;16. Hacettepe University School of Medicine, Ihsan Dogramaci Children's Hospital, Department of Pediatric Genetics, Ankara, Turkey;17. The Dubowitz Neuromuscular Centre, Department of Neurosciences, Great Ormond Hospital for Children, London, United Kingdom;18. Gazi University Hospital, Department of Pediatrics, Division of Neonatology Besevler, Ankara, Turkey;19. Unità Operativa Pediatria ‐Neonatologia – Nido, Ospedale San Martino, Oristano, Italy;20. Department of Pediatric Neurology, La Paz Hospital, Madrid, Spain;21. Discipline of Genetic Medicine, The University of Sydney, Sydney, Australia;22. Academic Department of Medical Genetics, The Children's Hospital at Westmead, Sydney, Australia;23. Clinica Sant’Anna, Cagliari, Italy |
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| Abstract: | Crisponi syndrome (CS) and cold‐induced sweating syndrome type 1 (CISS1) share clinical characteristics, such as dysmorphic features, muscle contractions, scoliosis, and cold‐induced sweating, with CS patients showing a severe clinical course in infancy involving hyperthermia associated with death in most cases in the first years of life. To date, 24 distinct CRLF1 mutations have been found either in homozygosity or in compound heterozygosity in CS/CISS1 patients, with the highest prevalence in Sardinia, Turkey, and Spain. By reporting 11 novel CRLF1 mutations, here we expand the mutational spectrum of CRLF1 in the CS/CISS1 syndrome to a total of 35 variants and present an overview of the different molecular and clinical features of all of them. To catalog all the 35 mutations, we created a CRLF1 mutations database, based on the Leiden Open (source) Variation Database (LOVD) system ( https://grenada.lumc.nl/LOVD2/mendelian_genes/variants ). Overall, the available functional and clinical data support the fact that both syndromes actually represent manifestations of the same autosomal‐recessive disorder caused by mutations in the CRLF1 gene. Therefore, we propose to rename the two overlapping entities with the broader term of Crisponi/CISS1 syndrome. |
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| Keywords: | CRLF1 CNTFR pathway Crisponi syndrome CISS1 |
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