Abstract
Spinal muscular atrophy (SMA) is caused by loss or mutations of the survival motor
neuron 1 gene (SMN1). Its highly homologous copy, SMN2, is present in all SMA cases and is a phenotypic modifier. There are cases where
asymptomatic siblings of typical SMA patients possess a homozygous deletion of SMN1 just like their symptomatic brothers or sisters. Plastin 3 (PLS3) when over expressed in lymphoblasts from females has been suggested to act as a
genetic modifier of SMA.
We studied PLS3 expression in four Spanish SMA families with discordant siblings haploidentical for
the SMA locus. We excluded PLS3 as a possible modifier in two of our families with female discordant siblings. In
the remaining two, we observed small differences in PLS3 expression between male and female discordant siblings. Indeed, we found that values
of PLS3 expression in lymphoblasts and peripheral blood ranged from 12 to 200-fold less than
those in fibroblasts. These findings warrant further investigation in motor neurons
derived from induced pluripotential stem cells of these patients.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Neuromuscular DisordersAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Spinal muscular atrophy – clinical and genetic correlations.Neuromuscul Disord. 1997; 7: 202-207
- SMN2 copy number predicts acute or chronic spinal muscular atrophy but does not account for intrafamilial variability in siblings.J Neurol. 2006; 253: 21-25
- Quantitative analyses of SMN1 and SMN2 based on real-time lightCycler PCR: fast and highly reliable carrier testing and prediction of severity of spinal muscular atrophy.Am J Hum Genet. 2002; 70: 358-368
- Correlation between SMN2 copy number and clinical phenotype of spinal muscular atrophy: three SMN2 copies fail to rescue some patients from the disease severity.J Neurol. 2002; 249: 1211-1219
- Mildly affected patients with spinal muscular atrophy are partially protected by an increased SMN2 copy number.Hum Genet. 2006; 119: 422-428
- Unusual pedigree patterns in seven families with spinal muscular atrophy; further evidence for the allelic model hypothesis.Clin Genet. 1986; 30: 145-149
- Discordant clinical outcome in type III spinal muscular atrophy sibships showing the same deletion pattern.Neuromuscul Disord. 1996; 6: 261-264
- Deletions of the survival motor neuron gene in unaffected siblings of patients with spinal muscular atrophy.Am J Hum Genet. 1995; 57: 805-808
- Molecular analysis of candidate genes on chromosome 5q13 in autosomal recessive spinal muscular atrophy: evidence of homozygous deletions of the SMN gene in unaffected individuals.Hum Mol Genet. 1995; 4: 1927-1933
- Unaffected patients with a homozygous absence of the SMN1 gene.Eur J Hum Genet. 2008; 16: 930-934
- Identification of proximal spinal muscular atrophy carriers and patients by analysis of SMNT and SMNC gene copy number.Am J Hum Genet. 1997; 60: 1411-1422
- A genetic and phenotypic analysis in Spanish spinal muscular atrophy patients with c.399_402del AGAG, the most frequently found subtle mutation in the SMN1 gene.Hum Mutat. 2003; 22: 136-143
- Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy.Science. 2008; 320: 524-527
- International SMA consortium meeting.Neuromuscul Disord. 1992; 2 ([26–28 June 1992, Bonn: Germany]): 423-428
- Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications.Arch Neurol. 1995; 52: 518-523
- A frame-shift deletion in the survival motor neuron gene in Spanish spinal muscular atrophy patients.Nat Genet. 1995; 11: 335-337
- Human plastin genes. Comparative gene structure, chromosome location, and differential expression in normal and neoplastic cells.J Biol Chem. 1993; 268: 2781-2792
- Association of plastin 3 expression with disease severity in spinal muscular atrophy only in postpubertal females.Arch Neurol. 2010; 67: 1252-1256
- Induced pluripotent stem cells from a spinal muscular atrophy patient.Nature. 2009; 457: 277-280
Article info
Publication history
Accepted:
March 24,
2011
Received in revised form:
February 25,
2011
Received:
January 6,
2011
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
