Association of copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein gene with the natural history in a Chinese spinal muscular atrophy cohort

J Child Neurol. 2015 Mar;30(4):429-36. doi: 10.1177/0883073814553271. Epub 2014 Oct 20.

Abstract

We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP.

Keywords: NAIP copy number; SMN2 copy number; modifier effect; spinal muscular atrophy; survival status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Asian People / genetics
  • Child, Preschool
  • China
  • Cohort Studies
  • DNA Copy Number Variations*
  • Humans
  • Infant
  • Infant, Newborn
  • Muscular Atrophy, Spinal / epidemiology
  • Muscular Atrophy, Spinal / genetics*
  • Neuronal Apoptosis-Inhibitory Protein / genetics*
  • Survival Analysis
  • Survival of Motor Neuron 2 Protein / genetics

Substances

  • NAIP protein, human
  • Neuronal Apoptosis-Inhibitory Protein
  • SMN2 protein, human
  • Survival of Motor Neuron 2 Protein