Correlation of SMN2, NAIP, p44, H4F5 and Occludin genes copy number with spinal muscular atrophy phenotype in Tunisian patients

ObjectivesSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder which is characterized by a high clinical variability with severe, intermediate, mild and adult forms. These forms are caused, in 95% of cases, by a homozygous deletion of exon 7 of SMN1 gene. Our purpose was the determination of a possible genotype–phenotype correlation between the copy number of SMN2, NAIP, p44, H4F5 and occludin genes localized in the same SMN1 region (5q13) and the severity of the disease in SMA Tunisian patients.Patients and methodsTwenty six patients affected by SMA were enrolled in our study. MLPA and QMPSF were used to measure copy numbers of these genes.ResultsWe found that 31.3% of type I patients carried one copy of SMN2, while all patients of other forms had at least 2 copies. NAIP was absent in 87.5% of type I patients. Furthermore, all SMA type I patients had one copy of H4F5. No correlation was found for p44 and occludin genes.ConclusionThere is a close relationship between SMN2, NAIP and H4F5 gene copy number and SMA disease severity, which is compatible with the previous reports.

► First study on SMA Tunisian patients focusing on SMN2, NAIP, p44, H4F5 and Occludin genes.
► Copy number variation of genes within SMN1 region influences SMA severity.
► SMN2 and NAIP genes are protector factors for SMA disease.
► H4F5 exon 1 deletion is frequently observed in type I SMA.
► Occludin gene does not seem to be involved in SMA phenotype.