Correlation Between Neuronal Apoptosis Inhibitory Protein (<i>NAIP</i>), <i>SMN2</i>, and SMA Phenotypes: A Tertiary Care Centre Experience From India

SMN2 copy number fails to answer variability in the SMA phenotype completely. We aimed to evaluate the copy number variation in NAIP and SMN2: c.859G>C and A-44G variants as disease modifiers and their correlation with the SMA phenotype. Based on the motor milestones achieved, patients with homozygous deletion of SMN1 exon 7 were classified into SMA Types I-IV. The copy numbers of SMN1 exon 8, SMN2, and NAIP were determined using the MLPA assay. Sanger sequencing was performed for the SMN2 variants. The cohort of 142 patients included nearly equal numbers of patients of SMA Types I, II, and III. The disease severity correlated with the SMN2 and NAIP copy number, with a lower copy number predicting a worse outcome. In addition, we evaluated the SMA genotype (SMN1 exon 8, SMN2 copy number, and NAIP copy number) as a predictor of SMA severity and found that most of the SMA Type I patients had a genotype of 0-2-0, SMA Type II patients had a genotype of 0-3-1, Type III patients had a genotype of 0-3-2 and 0-3-1, and Type IV patients had a genotype of 0-4-2. None of the patients from the cohort had the two modifier variants. The combined genotype of SMN1 exon 8 copy number-SMN2 copy number-NAIP copy number could accurately predict the SMA phenotype. The absence of SMN2: c.859G>C and A-44G variants in any of our patients points to the rarity of these variants in the Indian population.