Gender Effects on the Clinical Phenotype in Japanese Patients with Spinal Muscular Atrophy

Kobe J Med Sci. 2017 Oct 16;63(2):E41-E44.

Abstract

Background: Spinal muscular atrophy (SMA) is a neuromuscular disease caused by a mutation in SMN1. SMA is classified into three subtypes (types 1, 2, 3) based on achieved motor milestones. Although NAIP and SMN2 are widely accepted as SMA-modifying factors, gender-related modifying factors or gender effects on the clinical phenotype are still controversial.

Methods: A total of 122 Japanese patients with SMA, of which SMN1 was homozygously deleted, were analyzed from the perspective of the achieved motor milestone, NAIP status and SMN2 copy number.

Results: A predominance of male patients was observed in SMA type 3 (the walker group) without NAIP-deletion or with high SMN2 copy number (3 or 4 copies).

Conclusion: We suggest the presence of gender-related modifiers on disease severity in SMA patients. The modifiers may contribute only in the presence of NAIP and a high copy number of SMN2.

Keywords: NAIP; Spinal muscular atrophy; SMN2; clinical phenotype; gender.

MeSH terms

  • Asian People / genetics
  • Female
  • Gene Deletion
  • Gene Dosage
  • Humans
  • Japan
  • Male
  • Mobility Limitation
  • Muscular Atrophy, Spinal / classification
  • Muscular Atrophy, Spinal / diagnosis*
  • Muscular Atrophy, Spinal / genetics*
  • Neuronal Apoptosis-Inhibitory Protein / genetics
  • Phenotype
  • Sex Factors
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 2 Protein / genetics

Substances

  • NAIP protein, human
  • Neuronal Apoptosis-Inhibitory Protein
  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein