PUBLICATION

Distal motor neuropathy associated with novel EMILIN1 mutation

Authors
Iacomino, M., Doliana, R., Marchese, M., Capuano, A., Striano, P., Spessotto, P., Bosisio, G., Iodice, R., Manganelli, F., Lanteri, P., Orsini, A., Baldassari, S., Baratto, S., Fruscione, F., Prada, V., Broda, P., Tessa, A., Bertocci, G., Schenone, A., Colombatti, A., Minetti, C., Santorelli, F.M., Zara, F., Fiorillo, C.
ID
ZDB-PUB-200125-12
Date
2020
Source
Neurobiology of disease   137: 104757 (Journal)
Registered Authors
Keywords
Danio rerio, EMILIN1, Exome sequencing, Extracellular matrix, Fibroblast, Motor neuropathy
MeSH Terms
  • Adolescent
  • Animals
  • Fibroblasts/pathology*
  • Humans
  • Male
  • Membrane Glycoproteins/genetics*
  • Middle Aged
  • Mutation/genetics*
  • Phenotype
  • Skin/pathology*
  • Young Adult
  • Zebrafish
PubMed
31978608 Full text @ Neurobiol. Dis.
Abstract
Elastin microfibril interface-located proteins (EMILINs) are extracellular matrix glycoproteins implicated in elastogenesis and cell proliferation. Recently, a missense mutation in the EMILIN1 gene has been associated with autosomal dominant connective tissue disorder and motor-sensory neuropathy in a single family. We identified by whole exome sequencing a novel heterozygous EMILIN1 mutation c.748C>T [p.R250C] located in the coiled coil forming region of the protein, in four affected members of an autosomal dominant family presenting a distal motor neuropathy phenotype. In affected patient a sensory nerve biopsy showed slight and unspecific changes in the number and morphology of myelinated fibers. Immunofluorescence study of a motor nerve within a muscle biopsy documented the presence of EMILIN-1 in nerve structures. Skin section and skin derived fibroblasts displayed a reduced extracellular deposition of EMILIN-1 protein with a disorganized network of poorly ramified fibers in comparison with controls. Downregulation of emilin1a in zebrafish displayed developmental delay, locomotion defects, and abnormal axonal arborization from spinal cord motor neurons. The phenotype was complemented by wild-type zebrafish emilin1a, and partially the human wild-type EMILIN1 cRNA, but not by the cRNA harboring the novel c.748C>T [p.R250C]. These data suggest a role of EMILIN-1 in the pathogenesis of diseases affecting the peripheral nervous system.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping