A recent article study published in the Journal of Neuromuscular Diseases discussed that the DMD gene is the largest in human genome – with a total intron content exceeding 2.2 Mb. The authors reported that over decades since DMD was discovered, there have been numerous cases of pseudoexons (PEs) arising in the mature DMD transcripts of some individuals—either as the result of mutations or as low-frequency errors of the spliceosome.

On examining the diversity and commonalities of 58 DMD pseudoexons collated from published reports, great diversity in their sizes, locations and pathologies were observed. However, PEs arising either from no mutation or from mutations distal to the pseudoexon and its splice sites exhibited a high coincidence with predicted recursive splice sites in the DMD introns, suggesting that some such pseudoexons may arise from disruptions to recursive splicing regulation.

In inference, it was stated that this finding may represent an important new insight into the etiology of pseudoexons in DMD specifically, and human disease genes generally. A high frequency of PEs was detected, arising from deep intronic SNVs—that suggested a possible link between PEs induced by distal mutations and the regulation of recursive splicing.

Source: Journal of Neuromuscular Diseases. 2020;7(2):77-95. doi: 10.3233/JND-190431.