Association of Plastin 3 Expression With Disease Severity in Spinal Muscular Atrophy Only in Postpubertal Females

Abstract

To investigate the potential association of plastin 3 (PLS3) expression levels in the blood with disease severity in spinal muscular atrophy (SMA). Design: Measurement of PLS3 messenger RNA levels in the blood of patients with types I, II, and III SMA.

Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings

“…Although patients carry the same SMN1 deletion, the existence of differing clinical severity suggests that modifier genes may exist in SMA. So far, PLS3 and another gene, NRN1 , which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes . Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19‐fold upregulated in type III patients.…”

“…So far, PLS3 and another gene, NRN1, which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes. [10][11][12][13][14][15][17][18][19][20] Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19-fold upregulated in type III patients. Therefore, it is suggested that NRN1 may have a modifier effect on phenotype.…”

Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings

“…Although patients carry the same SMN1 deletion, the existence of differing clinical severity suggests that modifier genes may exist in SMA. So far, PLS3 and another gene, NRN1 , which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes . Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19‐fold upregulated in type III patients.…”

“…So far, PLS3 and another gene, NRN1, which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes. [10][11][12][13][14][15][17][18][19][20] Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19-fold upregulated in type III patients. Therefore, it is suggested that NRN1 may have a modifier effect on phenotype.…”

Ambulatory function in spinal muscular atrophy: Age-related patterns of progression

“…Our findings are in contrast to reports suggesting there may be genetic modifiers that are beneficial to female patients, particularly in the post-pubertal period. [ 17 ] These findings, however, should be interpreted with caution: while our overall study sample was largely balanced with respect to sex (56% male), nearly all of the type 3B patients (85.7%) were male. A greater representation of male patients in the milder cohort could have contributed to the overall sex differences in distance walked on the 6MWT.…”

A rare variant (c.863G>T) in exon 7 of SMN1 disrupts mRNA splicing and is responsible for spinal muscular atrophy

“…In addition, the plastin 3 (PLS3) gene at position Xq23 is protective in female SMA patients. [42][43][44][45] Our recent research 45 revealed that the PLS3 gene may have age-and gender-specific role (female protective) in the clinical severity in our SMA patients. So the male c.863G4T in exon 7 of SMN1 disrupts mRNA splicing Y Qu et al patient 3 exhibited a more serious phenotype than the female patients, a phenotypic difference that may partly be attributable to PLS3.…”

Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings

“…Although patients carry the same SMN1 deletion, the existence of differing clinical severity suggests that modifier genes may exist in SMA. So far, PLS3 and another gene, NRN1 , which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes . Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19‐fold upregulated in type III patients.…”

“…So far, PLS3 and another gene, NRN1, which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes. [10][11][12][13][14][15][17][18][19][20] Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19-fold upregulated in type III patients. Therefore, it is suggested that NRN1 may have a modifier effect on phenotype.…”

Ambulatory function in spinal muscular atrophy: Age-related patterns of progression

“…Our findings are in contrast to reports suggesting there may be genetic modifiers that are beneficial to female patients, particularly in the post-pubertal period. [ 17 ] These findings, however, should be interpreted with caution: while our overall study sample was largely balanced with respect to sex (56% male), nearly all of the type 3B patients (85.7%) were male. A greater representation of male patients in the milder cohort could have contributed to the overall sex differences in distance walked on the 6MWT.…”

A rare variant (c.863G>T) in exon 7 of SMN1 disrupts mRNA splicing and is responsible for spinal muscular atrophy

“…In addition, the plastin 3 (PLS3) gene at position Xq23 is protective in female SMA patients. [42][43][44][45] Our recent research 45 revealed that the PLS3 gene may have age-and gender-specific role (female protective) in the clinical severity in our SMA patients. So the male c.863G4T in exon 7 of SMN1 disrupts mRNA splicing Y Qu et al patient 3 exhibited a more serious phenotype than the female patients, a phenotypic difference that may partly be attributable to PLS3.…”

Transcript levels of plastin 3 and neuritin 1 modifier genes in spinal muscular atrophy siblings

“…Although patients carry the same SMN1 deletion, the existence of differing clinical severity suggests that modifier genes may exist in SMA. So far, PLS3 and another gene, NRN1 , which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes . Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19‐fold upregulated in type III patients.…”

“…So far, PLS3 and another gene, NRN1, which provides neuromuscular synaptogenesis, axonal branching, and regeneration, have been thought to act as modifier genes. [10][11][12][13][14][15][17][18][19][20] Moreover, in our preliminary study, on comparison of the transcriptome profiles of type I and type III fibroblasts, NRN1 expression was 5.19-fold upregulated in type III patients. Therefore, it is suggested that NRN1 may have a modifier effect on phenotype.…”

Ambulatory function in spinal muscular atrophy: Age-related patterns of progression

“…Our findings are in contrast to reports suggesting there may be genetic modifiers that are beneficial to female patients, particularly in the post-pubertal period. [ 17 ] These findings, however, should be interpreted with caution: while our overall study sample was largely balanced with respect to sex (56% male), nearly all of the type 3B patients (85.7%) were male. A greater representation of male patients in the milder cohort could have contributed to the overall sex differences in distance walked on the 6MWT.…”

A rare variant (c.863G>T) in exon 7 of SMN1 disrupts mRNA splicing and is responsible for spinal muscular atrophy

“…In addition, the plastin 3 (PLS3) gene at position Xq23 is protective in female SMA patients. [42][43][44][45] Our recent research 45 revealed that the PLS3 gene may have age-and gender-specific role (female protective) in the clinical severity in our SMA patients. So the male c.863G4T in exon 7 of SMN1 disrupts mRNA splicing Y Qu et al patient 3 exhibited a more serious phenotype than the female patients, a phenotypic difference that may partly be attributable to PLS3.…”