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

Abstract

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.