NAIP Gene Deletion and SMN2 Copy Number as Molecular Tools in Predicting the Severity of Spinal Muscular Atrophy

Abdel Nasser H Abd El Mutaleb; Fawziya A R Ibrahim; Fayed A K Megahed; Ahmed Atta; Bahy A Ali; Tarek E I Omar; Mona M Rashad

doi:10.1007/s10528-023-10657-6

NAIP Gene Deletion and SMN2 Copy Number as Molecular Tools in Predicting the Severity of Spinal Muscular Atrophy

Biochem Genet. 2024 Feb 22. doi: 10.1007/s10528-023-10657-6. Online ahead of print.

Authors

Abdel Nasser H Abd El Mutaleb¹, Fawziya A R Ibrahim², Fayed A K Megahed³, Ahmed Atta³, Bahy A Ali³, Tarek E I Omar⁴, Mona M Rashad¹

Affiliations

¹ Department of Applied Medical Chemistry, Medical Research Institute, University of Alexandria, Alexandria, Egypt.
² Department of Applied Medical Chemistry, Medical Research Institute, University of Alexandria, Alexandria, Egypt. Fawziya.ibrahim@alexu.edu.eg.
³ Department of Nucleic Acid Research, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications, Alexandria, Egypt.
⁴ Department of Pediatric Neurology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.

PMID: 38388850
DOI: 10.1007/s10528-023-10657-6

Abstract

Spinal muscular atrophy (SMA) is one of the most prevalent autosomal recessive illnesses with type I being the most severe type. Genomic alterations including survival motor neuron (SMN) copy number as well as deletions in SMN and Neuronal Apoptosis Inhibitory Protein (NAIP) are greatly implicated in the emergence of SMA. However, the association of such alterations with the severity of the disease is yet to be investigated. This study was directed to elucidate the molecular assessment of NAIP and SMN genomic alterations as a useful tool in predicting the severity of SMA among patients. This study included 65 SMA pediatric patients (30 type I and 35 type II) and 65 healthy controls. RFLP-PCR was employed to determine the genetic polymorphisms of the SMN1, SMN2, and NAIP genes. In addition, qRT-PCR was used to identify the expression of the SMN1 and SMN2 genes, and serum levels of creatine kinase were measured using a colorimetric method. DNA sequencing was performed on some samples to detect any single nucleotide polymorphisms in SMN1, SMN2, and NAIP genes. All SMA patients had a homozygous deficiency of SMN1 exon 7. The homozygous deficiency of SMN1 exons 7 and 8, with the deletion of NAIP exon 5 was found among the majority of Type I patients. In contrast, patients with the less severe condition (type II) had SMN1 exons 7 and 8 deleted but did not have any deletions in NAIP, additionally; 65.7% of patients had multiple copies of SMN2. Analysis of NAIP deletion alongside assessing SMN2 copy number might enhance the effectiveness of the diagnosis that can predict severity among Spinal Muscular Atrophy patients.

Keywords: NAIP deletions; SMN; Copy number; Molecular tools; SMA; Severity.