Clinical and molecular characteristics in three families with biallelic mutations in IGHMBP2

Neuromuscul Disord. 2016 Sep;26(9):570-5. doi: 10.1016/j.nmd.2016.06.457. Epub 2016 Jun 22.


Biallelic mutations in IGHMBP2 cause spinal muscular atrophy with respiratory distress type 1 (SMARD1) or Charcot-Marie-Tooth type 2S (CMT2S). We report three families variably affected by IGHMBP2 mutations. Patient 1, an 8-year-old boy with two homozygous variants: c.2T>C and c.861C>G, was wheelchair bound due to sensorimotor axonal neuropathy and chronic respiratory failure. Patient 2 and his younger sister, Patient 3, had compound heterozygous variants: c.983_987delAAGAA and c.1478C>T. However, clinical phenotypes differed markedly as the elder with sensorimotor axonal neuropathy had still unaffected respiratory function at 4.5 years, whereas the younger presented as infantile spinal muscular atrophy and died from relentless respiratory failure at 11 months. Patient 4, a 6-year-old girl homozygous for IGHMBP2 c.449+1G>T documented to result in two aberrant transcripts, was wheelchair dependent due to axonal polyneuropathy. The clinical presentation in Patients 1 and 3 were consistent with SMARD1, whereas Patients 2 and 4 were in agreement with CMT2S.

Keywords: Axonal polyneuropathy; CMT2S; IGHMBP2; SMARD1; Spinal muscular atrophy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Fatal Outcome
  • Female
  • Humans
  • Infant
  • Male
  • Mutation*
  • Phenotype
  • Respiratory Insufficiency / genetics
  • Respiratory Insufficiency / metabolism
  • Siblings
  • Spinal Muscular Atrophies of Childhood / genetics*
  • Spinal Muscular Atrophies of Childhood / metabolism*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • IGHMBP2 protein, human
  • Transcription Factors