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Neuromuscul Disord. 2015 Mar;25(3):222-4. doi: 10.1016/j.nmd.2014.11.007. Epub 2014 Nov 22.

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.

Author information

  • 1Neurology 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.
  • 2Neuropediatric Unit, Hospital Virgen de la Salud, Toledo, Spain.
  • 3Neuropediatric Unit, Complejo Universitario Hospitalario de Albacete, Albacete, Spain.
  • 4Department of Neurology, Complejo Universitario Hospitalario de Albacete, Albacete, Spain.
  • 5Department of Neurophysiology, Complejo Universitario Hospitalario de Albacete, Albacete, Spain.
  • 6Neurology 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.

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.

KEYWORDS:

ASAH1; Spinal muscular atrophy and progressive myoclonic epilepsy

PMID:
25578555
DOI:
10.1016/j.nmd.2014.11.007
[PubMed - indexed for MEDLINE]
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