Correlation Between the Motor Outcomes and SMN2 and NAIP Gene Copy Numbers Among North Indian Children with Spinal Muscular Atrophy.

BACKGROUND AND

OBJECTIVES

The clinical spectrum of spinal muscular atrophy (SMA) is heterogenous and depends on several factors. This study aimed to investigate the correlation between the motor outcomes and genetic modifiers of SMN1 gene.

METHODS

In this cross-sectional study, children with genetically confirmed diagnosis of SMA were enrolled. Motor outcomes were assessed using standard age-appropriate scale (Children's Hospital of Philadelphia infant test of neuromuscular disorders [CHOP], Revised Hammersmith Scale [RHS], and Medical Research Council [MRC] sum score). The copy numbers of SMN1, SMN2, and NAIP genes were estimated using multiplex ligation probe analysis.

RESULTS

Fifty children with SMA (26 males), with a mean age of 36 (17-84) months, were enrolled. Late-onset subtypes of SMA (types 2 and 3) constituted 78% of cases. The mean ± standard deviation (SD) CHOP score of children with type 1 SMA having one, two, and three copies of SMN2 gene exon 7 was 24 ± 5, 24 ± 8, and 35 ± 13, respectively. The mean ± SD RHS score of children with type 2 and 3 SMA was 32 ± 16, 29.4 ± 17, 37.8 ± 16, 56 ± 4 among children having two, three, four, and five copies of SMN2 gene exon 7. The RHS score and MRC sum score correlated significantly with SMN2 gene exon 7 copy numbers (p < 0.05). Homozygous deletion of NAIP gene was significantly higher in children with type 1 SMA compared to those with type 2 and 3 SMA (p value- 0.006).

CONCLUSIONS

The SMN2 gene exon 7 copy numbers correlate significantly with motor outcomes in children with SMA. NAIP gene deletion negatively influences the disease severity. NAIP gene can serve as a biomarker for disease prognostication.