TY - JOUR
T1 - Distal motor neuropathy associated with novel EMILIN1 mutation
T2 - Neurobiology of Disease
AU - Iacomino, M.
AU - Doliana, R.
AU - Marchese, M.
AU - Capuano, A.
AU - Striano, P.
AU - Spessotto, P.
AU - Bosisio, G.
AU - Iodice, R.
AU - Manganelli, F.
AU - Lanteri, P.
AU - Orsini, A.
AU - Baldassari, S.
AU - Baratto, S.
AU - Fruscione, F.
AU - Prada, V.
AU - Broda, P.
AU - Tessa, A.
AU - Bertocci, G.
AU - Schenone, A.
AU - Colombatti, A.
AU - Minetti, C.
AU - Santorelli, F.M.
AU - Zara, F.
AU - Fiorillo, C.
N1 - Cited By :1
Export Date: 26 March 2021
CODEN: NUDIE
Correspondence Address: Fiorillo, C.; Department of Neurosciences, Italy; email: chiara.fiorillo@edu.unige.it
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.nbd.2020.104757
DO - 10.1016/j.nbd.2020.104757
M3 - Article
VL - 137
JO - Neurobiol. Dis.
JF - Neurobiol. Dis.
SN - 0969-9961
M1 - 104757
ER -