Combined Genome Sequencing and RNA Analysis Reveals and Characterizes a Deep Intronic Variant in IGHMBP2 in a Patient With Spinal Muscular Atrophy With Respiratory Distress Type 1

Pediatr Neurol. 2021 Jan;114:16-20. doi: 10.1016/j.pediatrneurol.2020.09.011. Epub 2020 Sep 28.


Background: Pathogenic variants in the IGHMBP2 gene cause recessive spinal motor neuropathies of variable phenotype, including a predominantly distal motor impairment of Charcot-Marie-Tooth type 2S and the more severe condition of spinal muscular atrophy with respiratory distress type 1 in which infantile respiratory failure predominates.

Methods: We describe the first reported case of spinal muscular atrophy with respiratory distress type 1 caused by a novel deep intronic variant in IGHMBP2 (NM_002180c.712-610A>G).

Results: The variant was detected by whole genome sequencing. Reverse transcription-polymerase chain reaction and complimentary DNA sequencing were used to characterize the impact of the novel variant.

Conclusions: This report illustrates the utility in clinical practice of genome sequencing and RNA analysis, compared with exome sequencing alone.

Keywords: Clinical presentations; IGHMBP2 gene; Immunoglobulin μ-binding protein; Infantile neuromuscular disorders; SMARD1; Whole genome sequencing.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • DNA-Binding Proteins / genetics*
  • Humans
  • Infant
  • Male
  • Muscular Atrophy, Spinal / diagnosis
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / pathology
  • Muscular Atrophy, Spinal / physiopathology*
  • Respiratory Distress Syndrome, Newborn / diagnosis
  • Respiratory Distress Syndrome, Newborn / genetics*
  • Respiratory Distress Syndrome, Newborn / pathology
  • Respiratory Distress Syndrome, Newborn / physiopathology*
  • Sequence Analysis, RNA
  • Transcription Factors / genetics*
  • Whole Genome Sequencing


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

Supplementary concepts

  • Spinal muscular atrophy with respiratory distress 1