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A positive modifier of spinal muscular atrophy in the SMN2 gene.

Abstract：

:Spinal muscular atrophy (SMA) is a common autosomal-recessive motor neuron disease caused by the homozygous loss of the SMN1 gene. A nearly identical gene, SMN2, has been shown to decrease the severity of SMA in a dose-dependent manner. However SMN2 is not the sole phenotypic modifier, because there are discrepant SMA cases in which the SMN2 copy number does not explain the clinical phenotype. This report describes three unrelated SMA patients who possessed SMN2 copy numbers that did not correlate with the observed mild clinical phenotypes. A single base substitution in SMN2, c.859G>C,, was identified in exon 7 in the patients' DNA. We now show that the change creates a new exonic splicing enhancer element and increases the amount of full-length transcripts, thus resulting in the less severe phenotypes. This demonstrates that the c.859G>C substitution is a positive modifier of the SMA phenotype and that not all SMN2 genes are equivalent. We have shown not only that the SMA phenotype is modified by the number of SMN2 genes but that SMN2 sequence variations can also affect the disease severity.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Prior TW,Krainer AR,Hua Y,Swoboda KJ,Snyder PC,Bridgeman SJ,Burghes AH,Kissel JT

doi

10.1016/j.ajhg.2009.08.002

subject

Has Abstract

pub_date

2009-09-01 00:00:00

pages

408-13

issue

3

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(09)00345-0

journal_volume

85

pub_type

杂志文章

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