Congenital cytoplasmic body myopathy with survival motor neuron (SMN) gene deletion or Werdnig-Hoffman disease?

Spinal muscular atrophy (SMA), a devastating neurodegenerative disorder characterized by motor neuron loss and muscle atrophy, has been linked to mutations in the Survival Motor Neuron (SMN) gene. Based on an SMA model we developed in Drosophila, which displays features that are analogous to the human pathology and vertebrate SMA models, we functionally linked the fibroblast growth factor (FGF) signaling pathway to the Drosophila homologue of SMN, Smn. Here, we characterize this relationship and demonstrate that Smn activity regulates the expression of FGF signaling components and thus FGF signaling. Furthermore, we show that alterations in FGF signaling activity are able to modify the neuromuscular junction defects caused by loss of Smn function and that muscle-specific activation of FGF is sufficient to rescue Smn-associated abnormalities.

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Analysis of the mRNA transcripts of the survival motor neuron (SMN) gene in the tissue of an SMA fetus and the peripheral blood mononuclear cells of normals, carriers and SMA patients

Journal of the Neurological Sciences ◽

10.1016/s0022-510x(99)00325-1 ◽

2000 ◽

Vol 173 (2) ◽

pp. 147-153 ◽

Cited By ~ 24

Author(s):

Yuh-Jyh Jong ◽

Jan-Gowth Chang ◽

Shuan-Pei Lin ◽

Tzu-Yao Yang ◽

Jyh-Chwan Wang ◽

...

Keyword(s):

Motor Neuron ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Survival Motor Neuron ◽

Peripheral Blood Mononuclear ◽

Mrna Transcripts ◽

Blood Mononuclear Cells ◽

Smn Gene

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Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Macedonian Spinal Muscular Atrophy Patients

Balkan Journal of Medical Genetics ◽

10.2478/v10034-008-0007-z ◽

2007 ◽

Vol 10 (2) ◽

pp. 55-60 ◽

Cited By ~ 1

Author(s):

S Kocheva ◽

S Vlaski-Jekic ◽

M Kuturec ◽

G Efremov

Keyword(s):

Motor Neuron ◽

Neuronal Apoptosis ◽

Muscular Atrophy ◽

Survival Motor Neuron ◽

Type I ◽

Type Ii ◽

Inhibitory Protein ◽

Neuronal Apoptosis Inhibitory Protein ◽

Smn Gene ◽

Naip Gene

Molecular Analysis of Survival Motor Neuron and Neuronal Apoptosis Inhibitory Protein Genes in Macedonian Spinal Muscular Atrophy PatientsSpinal muscular atrophy (SMA) is classified according to the age of onset and severity of the clinical manifestations into: acute (Werding-Hoffman disease or type I), intermediate (type II) and juvenile (Kugelberg-Wilander disease or type III) forms. All three SMAs have been linked to markers at 5q11.2-q13.3. Two candidate genes deleted in SMA patients are the survival motor neuron (SMN) gene and the neuronal apoptosis inhibitory protein (NAIP) gene. We have performed molecular analyses of these genes in 30 unrelated Macedonian families (17 with type I, eight with type II and five with type III forms of the disease). Deletions of exons 7 and 8 of the SMN gene were found in 76.6% (23/30) of patients (94.1% in type I, 87.5% in type II). Among these 23 families, 19 had both exons deleted, while four had deletions only of exon 7. Deletions of exon 5 of the NAIP gene were found in 41.2% (7/17) patients with type I SMA and in 12.5% (1/8) of patients with type II SMA. No deletions of the SMN gene were found in 30 parents and 30 normal controls. We found 2/30 (6.7%) parents to be homozygous for the deletion of exon 5. Our data support the hypothesis that the telomeric SMN gene plays a major role in determining the clinical course of the disease, while the defects in the NAIP gene have only a modifying effect on the phenotype.

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Spinal Muscular Atrophy and Progressive Myoclonic Epilepsy: A Rare Association

Journal of Neurosciences in Rural Practice ◽

10.1055/s-0040-1721543 ◽

2021 ◽

Vol 12 (01) ◽

pp. 210-212

Author(s):

Divya M. Radhakrishnan ◽

Ritu Shree ◽

Govind Madhaw ◽

Rajat Manchanda ◽

Anita Mahadevan ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Motor Neuron ◽

Muscular Atrophy ◽

Survival Motor Neuron ◽

Myoclonic Epilepsy ◽

Motor Symptoms ◽

Rare Association ◽

Smn Gene ◽

Progressive Myoclonic Epilepsy ◽

Progressive Weakness

AbstractThe association of spinal muscular atrophy (SMA) with progressive myoclonic epilepsy, also known as “SMA plus,” is a unique syndrome linked to non-survival motor neuron (non-SMN) genes. The disease starts in childhood with progressive weakness and atrophy of muscles; myoclonic epilepsy develops during later childhood, after the onset of motor symptoms. In this report, we describe a case of SMN gene unrelated SMA and myoclonic epilepsy, supported by electrophysiological and neuropathological evidences.

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