NEW GENES IN NEUROMUSCULAR DISEASES: O.04 Heterozygous frameshift variants in hnRNPA2B1 cause a novel oculopharyngodistal muscular dystrophy

Abstract

Disrupting pathogenic variants in RNA-binding proteins such as TDP-43, hnRNPA2B1, FUS, TIA-1 are known to cause a spectrum of diseases, including frontotemporal dementia, amyotrophic lateral sclerosis, inclusion body myopathy, and/or distal myopathy. Using deep clinical phenotyping and exome sequencing, we identified six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia.