DICER1 Syndrome with an Intronic Germline Variant Causing Splice Alteration

Patients with DICER1 syndrome typically harbor a germline truncating variant in the coding region. Here, we report a case of DICER1 syndrome caused by an intronic germline variant. The patient was diagnosed with pleuropulmonary blastoma at the 3 years of age, and a somatic p.D1810Y, but not a germline variant in DICER1 was detected by whole-exome sequencing. After 13 years, he developed urogenital embryonal rhabdomyosarcoma with a somatic p.E1813D in DICER1 . Further analysis using complementary DNA DICER1 confirmed that a germline p.I813Ffs*24 and c.2437-15T>G caused the alteration. This report highlights the importance of a germline-dedicated analysis covering introns.