Background: Spinal muscular atrophy (SMA) is the most common autosomal recessive disorder in humans after cystic fibrosis. It is classified into five clinical grades based on age of onset and severity of the disease. Although SMN1 was identified as the SMA disease-determining gene, modifier genes mapped to 5q13 were affirmed to play a crucial role in determination of disease severity and used as a target for SMA therapy. In this study, we determined SMN2 copy number and NAIP deletion status in SMA Egyptian patients with different clinical phenotypes and had homozygous deletion of SMN1. We aimed at finding a prognostic genetic pattern including SMN1, SMN2, and NAIP gene genotypes to determine the clinical SMA type of the patient to help in genetic counseling and prenatal diagnosis. Results: Copy number variations (CNVs) of exon 7 of SMN2 gene were significantly decreased with the increase in disease severity. Homozygous deletion of exon 5 of NAIP was detected in 60% (12/20) of type I SMA and in 73% (8/ 11) of type III SMA cases. Combining the data of the SMN2 and NAIP genes showed 8 genotypes. Patients with D2 genotype (0 copies of NAIP and 2 copies of SMN2) were likely to have type I SMA. Type II SMA patients mostly had no homozygous deletion of NAIP and 2 copies of SMN2. However, patients with N3 genotype (> 1 copy of NAIP and 3 copies of SMN2) and patients with D3 genotype (0 copies of NAIP and > 3 copies of SMN2) had type III SMA. Conclusion: SMN2 and NAIP are the most important modifier genes whose copy numbers can affect the severity of SMA. We concluded that the combination of modifier genes to provide prognostic genetic pattern for phenotype determination is preferable than using CNVs of exon 7 of SMN2 gene only. CNVs of exon 7 of SMN2 are of high importance to predict patients' response to genetic therapy. On the other hand, deletion of exon5 of NAIP gene alone is not a sufficient predictor of SMA severity.

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Background: Until now, no laboratory test or test set can guarantee the diagnosis of multiple sclerosis (MS) at early disease stages, and the disease symptoms may interfere with many other disease conditions. Analyzing the expression of circulating miRNAs may provide a useful approach for early and differential MS diagnosis. The main objective is assessment of the potential of serum miR-23a, miR-155, and miR-572 to differentiate between MS and other neuroinflammatory diseases. Methods: Serum miRNAs were obtained from 37 MS patients and 25 healthy age-matched controls, along with patients with neuromyelitis optica spectrum disorder (NMOSD) [n = 13] and neuropsychiatric systemic lupus erythematosus (NPSLE) [n = 10]. miRNA expression levels were analyzed using real-time polymerase chain reaction (PCR) and pairwise comparisons were made to reveal the diagnostic/distinguishing potential of the analyzed miRNAs. Results: In the study cohort, the three investigated miRNAs failed to display significant dysregulation in MS patients. However, they could significantly discriminate patients with NMOSD and NPSLE [median (IQR): 8.1 (6.1–9.2) and 8.8 (7.9–9.7) for miR-23a, 7.5 (5.3–8.3) and 8.0 (7.5–9.5) for miR-155 and 6.9 (5.0–8.8) and 6.4 (5.3–8.8) for miR-572 in NMOSD and NPSLE, respectively] from healthy subjects [median (IQR): 3.4 (1.5–4.3), 3.1 (1.1–5.6) and 3.5 (1.7–5.6) for miR-23a, miR-155 and miR-572, respectively], with area under the curve (AUC) ≤0.8. Remarkably, miR-23a has been emerging as a prospective biomarker for differentiation of MS from NMOSD as well as NPSLE (AUC<0.9). The miRNA combined use contributed to enhanced diagnostic and discriminatory performance in the study groups. Conclusion: Certain miRNA expression levels would contribute to discriminating MS from other neuroinflammatory diseases.

Background Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease representing the most prevalent monogenic cause of infant mortality. It results from the loss of SMN1 gene, but retention of its paralog SMN2 whose copy number can modulate the disease severity and guide the therapeutic regimen. Methods For SMA molecular analysis, 236 unrelated Egyptian patients were enrolled at our institution. The Multiplex ligation-dependent probe amplification analysis (MLPA) was applied to investigate the main genetic defect in the enrolled patients (SMN1 loss) and to determine a possible genotype–phenotype correlation between the copy number of other genes in the SMN locus (5q13.2) and disease severity in Egyptian patients with SMA. A small cohort of healthy subjects (n = 57) was also included to investigate the possible differences in the distributions of SMN2 and NAIP genes between patients and healthy individuals. Results Disease diagnosis was confirmed in only 148 patients (62.7%) highlighting the clinical overlapping of the disease and emphasizing the importance of molecular diagnosis. In patients with homozygous SMN1 loss, the disease was mediated by gene deletion and conversion in 135 (91.2%) and 13 (8.8%) patients, respectively. In the study cohort, SMN2 and NAIP copy numbers were inversely correlated with disease severity. However, no significant association was detected between GTF2H2A and SERF1B copy numbers and patient phenotype. Significant differences were demonstrated in the copy numbers of SMN2 and NAIP between SMA patients and healthy subjects. Conclusion Molecular analysis of SMA is essential for disease diagnosis. Consistent with previous studies on other populations, there is a close relationship between SMN2 and NAIP copy numbers and clinical phenotype. Additionally, potential differences in these two genes distributions are existing between patients and healthy subjects. National program for carrier screening should be established as a preventive disease strategy. On the other hand, neonatal testing would provide accurate estimation for disease incidence.