Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings.
BACKGROUND
In single gene disorders, patients with the same genotype may have variations in severity. One of the main factors affecting disease severity is modifier genes. Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by degeneration of alpha motor neurons. Plastin 3 (PLS3) is a phenotypic modifier of SMA, and neuritin 1 (NRN1) has also been suggested as a possible modifier gene. The aim of the present study was therefore to analyze PLS3 and NRN1 expression in SMA siblings in four families.


METHODS
The study group consisted of four SMA families with seven with discordant phenotype and two affected siblings. Total RNA was isolated from whole blood. PLS3 and NRN1 expression was analyzed on quantitative real-time polymerase chain reaction.


RESULTS
In family 1 only NRN1 expression was increased in the mildly affected sister. In family 2 only PLS3 had a modifier effect. Family 3, which had type III siblings with identical clinical phenotypes, had similar PLS3 expression between the siblings but no NRN1 expression. In family 4, neither PLS3 nor NRN1 had any correlation with severity.


CONCLUSIONS
On analysis of the expression of NRN1 in SMA patients for the first time, NRN1 could be a potential modifier gene. PLS3 expression does not always modify SMA phenotype. In patients with no modifier effect of known genes, genome sequencing and transcriptome analysis are promising for the identification of novel modifiers and understanding of SMA pathophysiology.
Department of Medical Biology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.
İnci Hande
İH
Yener
Department of Pediatric Neurology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.
Haluk
H
Topaloglu
Department of Neurology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.
Sevim
S
Erdem-Özdamar
Department of Medical Biology, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara, Turkey.
Didem
D
Dayangac-Erden
D000293:Adolescent; D002648:Child; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D060045:Genes, Modifier; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D035781:Siblings; D055815:Young Adult
D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C484539:NRN1 protein, human; D009479:Neuropeptides; C026742:plastin
modifier gene; neuritin; plastin 3; spinal muscular atrophy; transcript