Lisanne Woudt1, Gabriella A Di Capua2, Martin Krahn3,4, Claudia Castiglioni5, Ricardo Hughes1, Mario Campero1, Alejandra Trangulao6, Patricio González-Hormazábal2, Raúl Godoy-Herrera2, Nicolas Lévy3,4, Jon Andoni Urtizberea7, Lilian Jara2, Jorge A Bevilacqua1,6. 1. Unidad Neuromuscular, Departamento de Neurología y Neurocirugía, Hospital Clínico Universidad de Chile, Santos Dumont 999, 2do. piso, Sector E. Independencia, 8380456, Santiago, Chile. 2. Programa de Genética Humana, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile. 3. Aix Marseille Université, INSERM, Medical Genetics and Functional Genomics, Unité Mixte de Recherche_S 910, Marseille, France. 4. Assistance Publique - Hôpitaux de Marseille, Département de Génétique Médicale, Hôpital Timone Enfants, Marseille, France. 5. Unidad de Neurología, Departamento de Pediatría, Clínica Las Condes, Santiago, Chile. 6. Programa Anatomía y Biología del Desarrollo, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile. 7. Unité Neuromusculaire, Hôpital Marin de Hendaye, Assistance Publique - Hôpitaux de Paris, Hendaye, France.
Abstract
INTRODUCTION: Understanding the natural history of dysferlinopathy is essential to design and quantify novel therapeutic protocols. Our aim in this study was to assess, clinically and functionally, a cohort of patients with dysferlinopathy, using validated scales. METHODS: Thirty-one patients with genetically confirmed dysferlinopathy were assessed using the motor function measure (MFM), Modified Rankin Scale (MRS), Muscle Research Council (MRC) scale, serum creatine kinase (CK) assessment, baseline spirometry data, and echocardiographic and electrophysiologic studies. RESULTS: MFM and MRC scores showed a significant negative correlation with disease duration and inverse correlation with MRS, but not with onset age, clinical phenotype, or CK levels. Percent forced vital capacity (%FVC) correlated negatively with disease duration and onset age. Eight known pathogenic mutations were identified recurrently, 4 of which accounted for 79% of the total. CONCLUSIONS: The results suggest that MFM is a reliable outcome measure that may be useful for longitudinal follow-up in dysferlinopathy. Recurrent mutations suggest a founder effect in the Chilean population.
INTRODUCTION: Understanding the natural history of dysferlinopathy is essential to design and quantify novel therapeutic protocols. Our aim in this study was to assess, clinically and functionally, a cohort of patients with dysferlinopathy, using validated scales. METHODS: Thirty-one patients with genetically confirmed dysferlinopathy were assessed using the motor function measure (MFM), Modified Rankin Scale (MRS), Muscle Research Council (MRC) scale, serum creatine kinase (CK) assessment, baseline spirometry data, and echocardiographic and electrophysiologic studies. RESULTS: MFM and MRC scores showed a significant negative correlation with disease duration and inverse correlation with MRS, but not with onset age, clinical phenotype, or CK levels. Percent forced vital capacity (%FVC) correlated negatively with disease duration and onset age. Eight known pathogenic mutations were identified recurrently, 4 of which accounted for 79% of the total. CONCLUSIONS: The results suggest that MFM is a reliable outcome measure that may be useful for longitudinal follow-up in dysferlinopathy. Recurrent mutations suggest a founder effect in the Chilean population.
Authors: Ursula Moore; Marni Jacobs; Meredith K James; Anna G Mayhew; Roberto Fernandez-Torron; Jia Feng; Avital Cnaan; Michelle Eagle; Karen Bettinson; Laura E Rufibach; Robert Muni Lofra; Andrew M Blamire; Pierre G Carlier; Plavi Mittal; Linda Pax Lowes; Lindsay Alfano; Kristy Rose; Tina Duong; Katherine M Berry; Elena Montiel-Morillo; Irene Pedrosa-Hernández; Scott Holsten; Mohammed Sanjak; Ai Ashida; Chikako Sakamoto; Takayuki Tateishi; Hiroyuki Yajima; Aurélie Canal; Gwenn Ollivier; Valerie Decostre; Juan Bosco Mendez; Nieves Sánchez-Aguilera Praxedes; Simone Thiele; Catherine Siener; Jeanine Shierbecker; Julaine M Florence; Bruno Vandevelde; Brittney DeWolf; Meghan Hutchence; Richard Gee; Juliana Prügel; Elke Maron; Heather Hilsden; Hanns Lochmüller; Ulrike Grieben; Simone Spuler; Carolina Tesi Rocha; John W Day; Kristi J Jones; Diana X Bharucha-Goebel; Emmanuelle Salort-Campana; Matthew Harms; Alan Pestronk; Sabine Krause; Olivia Schreiber-Katz; Maggie C Walter; Carmen Paradas; Jean-Yves Hogrel; Tanya Stojkovic; Shin'ichi Takeda; Madoka Mori-Yoshimura; Elena Bravver; Susan Sparks; Jordi Díaz-Manera; Luca Bello; Claudio Semplicini; Elena Pegoraro; Jerry R Mendell; Kate Bushby; Volker Straub Journal: Neurology Date: 2019-01-09 Impact factor: 9.910
Authors: Jens A Petersen; Thierry Kuntzer; Dirk Fischer; Maja von der Hagen; Angela Huebner; Veronika Kana; Johannes A Lobrinus; Wolfram Kress; Elisabeth J Rushing; Michael Sinnreich; Hans H Jung Journal: BMC Neurol Date: 2015-10-06 Impact factor: 2.474
Authors: Luis A Cea; Jorge A Bevilacqua; Christian Arriagada; Ana María Cárdenas; Anne Bigot; Vincent Mouly; Juan C Sáez; Pablo Caviedes Journal: BMC Cell Biol Date: 2016-05-24 Impact factor: 4.241