RNAseq of skeletal muscle. Homo sapiens

Oculopharyngodistal myopathy (OPDM) is an inherited myopathy manifesting with ptosis, dysphagia, distal weakness and with rimmed vacuoles and intranuclear inclusions on muscle biopsy. In recent years groups have identified four different genetic causes of oculopharynogdistal myopathy (OPDM) in Asian populations. These include CGG expansions in the 5UTR of LRP12, GIPC1, NOTCH2NLC and most recently RILPL1. However, there remain families and patients with a clinical diagnosis of OPDM whom remain without a molecular diagnosis. In this study we describe identification of CCG expansions in six ODPM families of European ancestry. In two large Australian OPDM families, using a combination of linkage studies, short-read WGS and targeted ONT sequencing, we identified CCG expansions in the 5UTR of ABCD3. A third small Australian OPDM family was also subsequently identified to harbour CCG expansions at this same locus. Independently, the ABCD3 CCG expansion was identified in three individuals from two unrelated UK families diagnosed with OPDM and one sporadic case from France.RNAseq of skeletal muscle showed that ABCD3 was overexpressed in 3 ODPM patient biopsies compared to healthy controls and patient with other forms of neuromuscular disorders.