title: Phenotypical features of a new dominant GDAP1 pathogenic variant (p.R226del) in axonal Charcot-Marie-Tooth disease.
abstract: There are few reports on axonal CMT due to dominant GDAP1 mutations. We describe two unrelated Spanish families with a dominant axonal CMT. A novel in frame GAA deletion in exon 5 of the GDAP1 gene (c.677_679del; p.R226del) was identified in both families. Disease onset varied from early childhood to adulthood. Affected family members complained of distal lower limb weakness, cramps and foot deformities with variable CMTNS score in both families. Several individuals were asymptomatic or had paraesthesia only, however neurological examination and nerve conduction studies demonstrated neuropathic signs. Transfection of HeLa cells with the p.R226del mutation led to an increased mitochondrial aggregation. We report an AD-CMT2K with large phenotypic variability due to a novel dominant GDAP1 variant. This is the second founder GDAP1 pathogenic variant reported in Spain.
authors.affiliation: Department of Neurology, Hospital Clínico, Santiago de Compostela, Spain; Neurogenetics Research Group, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain. Electronic address: ainat.tania@hotmail.com.
authors.forename: Tania
authors.initials: T
authors.lastname: García-Sobrino
authors.affiliation: Neurogenetics Research Group, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Blanco-Arias
authors.affiliation: Institut de Recerca Sant Joan de Déu, CIBERER, Barcelona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Palau
authors.affiliation: Department of Genomics and Translational Genetics, Centro de Investigación Príncipe Felipe, Valencia, Spain; Unit for Genetics and Genomics of Neuromuscular and Neurodegenerative Diseases, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Espinós
authors.affiliation: Department of Genomics and Translational Genetics, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ramirez
authors.affiliation: Instituto de Biomedicina de Valencia (CSIC), CIBERER, Valencia, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Estela
authors.affiliation: Department of Pathology, Hospital Universitario de Vigo, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: San Millán
authors.affiliation: Department of Neurology, Hospital Clínico, Santiago de Compostela, Spain; Neurogenetics Research Group, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Arias
authors.affiliation: Neurogenetics Research Group, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain; Fundación Pública Galega de Medicina Xenómica, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Spain. Electronic address: ssobrido@gmail.com.
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Sobrido
authors.affiliation: Department of Neurology, Hospital Clínico, Santiago de Compostela, Spain; Neurogenetics Research Group, Instituto de Investigaciones Sanitarias (IDIS), Santiago de Compostela, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Pardo
mesh_terms: D000328:Adult; D000368:Aged; D001369:Axons / Q000473:pathology*; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005192:Family Health; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000473:pathology / Q000648:ultrastructure; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D013030:Spain; D013497:Sural Nerve / Q000378:metabolism; D014162:Transfection; D055815:Young Adult
chemical_list: C118663:GDAP protein; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C084008:TOMM20 protein, human
keywords: CMT2K; Charcot-Marie-Tooth; GDAP1 variants; Hereditary neuropathy; Pathogenic mutation