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.
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.
['Bodle|Ethan E|EE|', 'Zhu|Wenmiao|W|', 'Velez-Bartolomei|Frances|F|', 'Tesi-Rocha|Ana|A|', 'Liu|Pengfei|P|', 'Bernstein|Jonathan A|JA|']
D004268:DNA-Binding Proteins D006801:Humans D007223:Infant D008297:Male D009134:Muscular Atrophy, Spinal D012127:Respiratory Distress Syndrome, Newborn D017423:Sequence Analysis, RNA D014157:Transcription Factors D000073336:Whole Genome Sequencing
IGHMBP2 gene Whole genome sequencing Clinical presentations Immunoglobulin μ-binding protein Infantile neuromuscular disorders SMARD1