A novel DICER1 mutation identified in a female with ovarian Sertoli-Leydig cell tumor and multinodular goiter: a case report

INTRODUCTION: Germ-line mutations in the micro-ribonucleic acid processing gene DICER1 have been shown to predispose to a subset of benign tumors susceptible to malignant transformation, including ovarian Sertoli-Leydig cell tumor, nontoxic multinodular goiter, multilocular cystic nephroma and pleuropulmonary blastoma, which can occur in children and young adults. This may be due to reduced Dcr-1 homolog expression in carriers of germline mutations, which causes impairment of micro-ribonucleic acid processing and deregulates the growth and differentiation of target cells, leading to an increased risk of tumorigenesis. Many carriers of germ-line DICER1 mutations remain unaffected, but development of tumors within carriers is associated with varying prognoses. CASE PRESENTATION: Despite the Dcr-1 homolog syndrome phenotype being incompletely defined, a DICER1 mutation was suspected when a girl (case 1 patient) of Danish ethnicity presented with both an ovarian Sertoli-Leydig cell tumor and a multinodular goiter at the age of 13 years. In addition, family history included a male sibling (case 2 patient) who also had a multinodular goiter and had undergone a hemithyroidectomy at the age of 14 years. Subsequent DICER1 screening of the girl identified two novel mutations in exon 21 - a nonsense (c.3647C>A, p.Ser1216*) and a missense (c.3649T>A, p.Tyr1217Asn) mutation. The siblings had inherited the mutations from their father and paternal grandfather, which both currently were asymptomatic, indicating reduced penetrance of the nonsense mutation. Analysis of the parents revealed that the mutations were present in cis, making the contribution of the missense mutation less significant. CONCLUSION: We report a novel pathogenic DICER1 mutation (p.Ser1216*) in a Danish family associated with ovarian Sertoli-Leydig cell tumor and a multinodular goiter. A multinodular goiter was diagnosed in the siblings during childhood. Clinicians should be aware of a potential germ-line DICER1 mutation when evaluating multinodular goiter in young patients with or without a family history of thyroid diseases.