Spinal Müsküler Atrofi Patogenezinde Rol Alan Genetik Düzenleyicilerin İfade Analizi

Abstract

Childhood- onset spinal muscular atrophy (SMA) is an autosomal recessive disorder, which leads to alpha motor neuron degeneration. Although 95-98 % of the patients have homozygous deletions in exon 7 and 8 SMN1 gene, patients with different clinical severity suggest that modifier genes, which affect the phenotype, may exist in SMA. This study aims to investigate plastin 3 (PLS3) and neuritin 1 (NRN1) gene expression levels in blood, 11 SMA patients with different types, ages and in 4 families with different clinical characteristics. According to gene expression results, in pediatric type III group, similar PLS3 gene expression levels (3.5-3.6 fold) were detected in H6 and H8, who had similar clinical symptoms. However, in mildly affected H1, lower PLS3 and NRN1 gene expression levels were determined; therefore it was thought that modifier genes other than PLS3 and NRN1 may affect this patient?s phenotype. In type III SMA group, in two mildly affected patients (H5, H9), high PLS3 and NRN1 gene expression levels (0.9-1.6 fold) were identified. In two patients, both PLS3 and NRN1 were thought to play a modifier role. In H3 and H4 patients that have similar levels of muscle weakness, similar PLS3 and NRN1 gene expression pattern was identified. However, in H2 who showed similar clinical symptoms with H3 and H4, higher NRN1 gene expression level was detected. It was thought that NRN1 gene may be effective on the phenotype of this patient. On the contrary in one type II and two type I SMA patients, high PLS3 expression levels (2.1- 2.6 fold) were determined. In addition, in family 1, NRN1 expression levels showed 1.4 fold increase in mildly affected sibling than his severely affected brother. In family 2, higher PLS3 and NRN1 gene expression levels (1.8-2.7 fold) were detected in mildly affected sibling compared to his severely affected brothers. In family 3, similar PLS3 expression levels were detected in siblings who had similar clinical severity. In family 4, it was thought that modifier genes other than PLS3 and NRN1 may be effective. In this study, PLS3 and NRN1 gene expression levels and their modifying roles were investigated in SMA patients that have deletions in SMN1 gene.