Charcot-Marie-Tooth disease due to MORC2 mutations in Spain
Por:
Sivera, R, Lupo, V, Frasquet, M, Argente-Escrig, H, Alonso-Perez, J, Diaz-Manera, J, Querol, L, Garcia-Romero, MD, Pascual, SI, Garcia-Sobrino, T, Paradas, C, Vazquez-Costa, JF, Muelas, N, Millet, E, Vilchez, JJ, Espinos, C, Sevilla, T
Publicada:
1 sep 2021
Ahead of Print:
1 jul 2021
Resumen:
Background and purpose MORC2 mutations have been described as a rare cause of axonal Charcot-Marie-Tooth disease (CMT2Z). The aim of this work was to determine the frequency and distribution of these mutations throughout Spain, to provide a comprehensive phenotypical description and, if possible, to establish a genotype-phenotype correlation. Methods Retrospectively, data on patients diagnosed with CMT2Z in Spain were collected and clinical, electrophysiological and muscle imaging information were analysed. Results Fifteen patients with CMT2Z were identified throughout Spain, seven of them belonging to a single kindred, whilst the rest were sporadic. The most common mutation was p.R252W, and four new mutations were identified. Eleven patients were categorized as having a scapuloperoneal phenotype, with asymmetric muscle weakness, early proximal upper limb involvement and frequent spontaneous muscular activity with distal sensory impairment and pes cavus, whilst two presented with a more classic length dependent sensory motor phenotype. This distinction was corroborated by the distribution of muscle fatty infiltration in muscle imaging. Two other patients were classified as having a neurodevelopmental phenotype consisting in congenital or early onset, delay in motor milestones, and global developmental delay in one of them. Nerve conduction studies revealed an unequivocally axonal neuropathy with frequent spontaneous activity, and serum creatine kinase levels were increased in 50% of the patients. Conclusions MORC2 mutations are a rare cause of CMT in Spain, but in-depth phenotyping reveals a recognizable phenotypic spectrum that will be clinically relevant for future identification of this disease.
Filiaciones:
Sivera, R:
Hosp Francesc Borja, Dept Neurol, Gandia, Spain
Lupo, V:
Ctr Invest Principe, Unit Rare Neurodegenerat Dis Felipe, Valencia, Spain
Hosp Univ & Politecn La Fe, Dept Neurol, Neuromuscular Dis Unit, Valencia, Spain
Inst Invest Sanitaria La Fe, Neuromuscular & Ataxias Res Grp, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Frasquet, M:
Hosp Univ & Politecn La Fe, Dept Neurol, Neuromuscular Dis Unit, Valencia, Spain
Inst Invest Sanitaria La Fe, Neuromuscular & Ataxias Res Grp, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Argente-Escrig, H:
Hosp Univ & Politecn La Fe, Dept Neurol, Neuromuscular Dis Unit, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Alonso-Perez, J:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp Santa Creu & Sant Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Diaz-Manera, J:
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Hosp Santa Creu & Sant Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Newcastle Univ, Translat & Clin Res Inst, John Walton Muscular Dystrophy Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England
Querol, L:
Hosp Santa Creu & Sant Pau, Dept Neurol, Neuromuscular Dis Unit, Barcelona, Spain
Univ Autonoma Barcelona, Barcelona, Spain
Garcia-Romero, MD:
Hosp Univ La Paz, Neuropaediat Dept, Madrid, Spain
Univ Autonoma Madrid, Dept Pediat, Madrid, Spain
Pascual, SI:
Hosp Univ La Paz, Neuropaediat Dept, Madrid, Spain
Univ Autonoma Madrid, Dept Pediat, Madrid, Spain
Garcia-Sobrino, T:
Complexo Hosp Univ Santiago De Compostela, Dept Neurol, Santiago De Compostela, Spain
Paradas, C:
Hosp Univ Virgen Rocio, Dept Neurol, Seville, Spain
Vazquez-Costa, JF:
Hosp Univ & Politecn La Fe, Dept Neurol, Neuromuscular Dis Unit, Valencia, Spain
Inst Invest Sanitaria La Fe, Neuromuscular & Ataxias Res Grp, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain
Univ Valencia, Dept Med, Valencia, Spain
Muelas, N:
Hosp Univ & Politecn La Fe, Dept Neurol, Neuromuscular Dis Unit, Valencia, Spain
Inst Invest Sanitaria La Fe, Neuromuscular & Ataxias Res Grp, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Millet, E:
Hosp Univ & Politecn La Fe, Dept Clin Neurophysiol, Neuromuscular Dis Unit, Valencia, Spain
Vilchez, JJ:
Hosp Univ & Politecn La Fe, Dept Neurol, Neuromuscular Dis Unit, Valencia, Spain
Inst Invest Sanitaria La Fe, Neuromuscular & Ataxias Res Grp, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Valencia, Dept Med, Valencia, Spain
Espinos, C:
Ctr Invest Principe, Unit Rare Neurodegenerat Dis Felipe, Valencia, Spain
Sevilla, T:
Hosp Univ & Politecn La Fe, Dept Neurol, Neuromuscular Dis Unit, Valencia, Spain
Inst Invest Sanitaria La Fe, Neuromuscular & Ataxias Res Grp, Valencia, Spain
Inst Salud Carlos III, Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain
Univ Valencia, Dept Med, Valencia, Spain
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