Analysis of DICER1 in familial and sporadic cases of transposition of the great arteries

Objective We previously identified a pathogenic germline DICER1 variant in a child with transposition of the great arteries who was a member of a family with DICER1 syndrome. In view of a report linking Dicer1 knockout in murine cardiomyocytes to cardiac outflow defects, we investigated the involvement of DICER1 in transposition of the great arteries. Design We used Fluidigm access array followed by next generation sequencing to screen for variants in the coding exons, their exon/intron boundaries and the 3′ untranslated region of DICER1 in patient DNA. Cases Germline DNA was collected from 129 patients with either sporadic or familial forms of transposition of the great arteries from two sites in Australia and Italy. Results Most cases (85%) did not have any germline DICER1 variants. In the remaining 15% of cases, we identified 16 previously reported variants (5 synonymous, 6 intronic, and 5 missense) and 2 novel variants (1 intronic and 1 missense). None of the identified variants were predicted to be pathogenic. Conclusions Here, we report that neither likely pathogenic nor pathogenic variants in DICER1 appear to play a major role in transposition of the great arteries.