title: Uniparental disomy as a cause of spinal muscular atrophy and progressive myoclonic epilepsy: phenotypic homogeneity due to the homozygous c.125C>T mutation in ASAH1.
abstract: Spinal muscular atrophy and progressive myoclonic epilepsy (SMAPME, OMIM#159950) is a rare autosomal recessive disorder characterized by the combination of progressive myoclonic epilepsy and muscular weakness due to lower motor neuron disease. Mutations in ASAH1, previously associated only to Farber disease, have been recently described in seven patients with SMAPME. A homozygous c.125C>T mutation was initially found in six patients with a clinical homogeneous phenotype. A heterozygous compound mutation found in an additional patient has broadened the clinical and genetic spectrum of clinical SMAPME. We report a new case of a 13-year-old girl with SMAPME with the homozygous ASAH1 c.125C>T mutation, unique in that it is due to paternal uniparental disomy. She experienced muscle weakness from the age of three due to lower motor neuron involvement that lead to severe handicap and onset in late childhood of a progressive myoclonic epilepsy. This clinical picture fully overlaps with that of previously reported patients with this mutation and supports our view that the clinical phenotype associated with the homozygous c.125C>T mutation constitutes a clinically homogenous and recognizable disease.
authors.affiliation: Neurology Lab and Epilepsy Unit, Department of Neurology, IIS- Fundación Jiménez Díaz, UAM, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Beatriz G
authors.initials: BG
authors.lastname: Giráldez
authors.affiliation: Neurology Lab and Epilepsy Unit, Department of Neurology, IIS- Fundación Jiménez Díaz, UAM, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Guerrero-López
authors.affiliation: Neurology Lab and Epilepsy Unit, Department of Neurology, IIS- Fundación Jiménez Díaz, UAM, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Ortega-Moreno
authors.affiliation: Neuropediatric Unit, Hospital Virgen de la Salud, Toledo, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Verdú
authors.affiliation: Neuropediatric Unit, Complejo Universitario Hospitalario de Albacete, Albacete, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Carrascosa-Romero
authors.affiliation: Neuropediatric Unit, Hospital Virgen de la Salud, Toledo, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: García-Campos
authors.affiliation: Department of Neurology, Complejo Universitario Hospitalario de Albacete, Albacete, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: García-Muñozguren
authors.affiliation: Department of Neurophysiology, Complejo Universitario Hospitalario de Albacete, Albacete, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Pardal-Fernández
authors.affiliation: Neurology Lab and Epilepsy Unit, Department of Neurology, IIS- Fundación Jiménez Díaz, UAM, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain. Electronic address: joseserratosa@me.com.
authors.forename: José M
authors.initials: JM
authors.lastname: Serratosa
mesh_terms: D055573:Acid Ceramidase / Q000235:genetics*; D000293:Adolescent; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D009154:Mutation; D020191:Myoclonic Epilepsies, Progressive / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D024182:Uniparental Disomy
chemical_list: C526693:ASAH1 protein, human; D055573:Acid Ceramidase
keywords: ASAH1; Spinal muscular atrophy and progressive myoclonic epilepsy