ESPE Abstracts (2018) 89 P-P1-261

ESPE2018 Poster Presentations Thyroid P1 (22 abstracts)

A Novel DICER1 Mutation Identified in a Family with the Multinodular Goiter of Children

Keisuke Nagasaki a , Nao Shibata a , Hiromi Nyuzuki a , Sunao Sasaki a , Yohei Ogawa a , Takahiko Kogai b & Akira Hishinuma b

aDepartment of Pediatrics, Niigata University Medical and Dental Hospital, Niigata, Japan; bDepartment of Infection Control and Clinical Laboratory Medicine, Dokkyo Medical University, Tochigi, Japan

Background: Nontoxic multinodular goiter (MNG) is frequently encountered in the general population, but little is known about the underlying genetic susceptibility to this disease. Recently, germline mutations in DICER1, a gene that codes for an RNase III endoribonuclease, have been identified in familial MNG with and without Sertoli-Leydig cell tumor of the ovary.

Objective: We reporteda family exhibiting various thyroid diseases in which a DICER1 germline mutation was revealed first in the proband with the childhood onset MNG and subsequently in the family members.

Patients: The patient presented to our hospital with a cervical mass at the age of 6 years. Thyroid ultrasonography revealed a mixed type tumor with the size of 15 mm in the right lobe, showing tendency to grow. During the following two years, two nodules appeared in the right lobe, one in the isthmus and another in the left lobe. Fine-needle aspiration biopsy of the nodule in the right lobe with unclear boundaries showed that the nodule was benign. A diagnosis of MNG was made. Total thyroidectomy was performed at the age of 8 years because of a significant increase in thyroglobulin level, an increase in tumor mass, and discomfort during swallowing. Her mother had her thyroid nodule removed at the age of 15 years, and a total thyroidectomy was performed on a cervical tumor that was diagnosed as poorly differentiated thyroid carcinoma and MNG when she was 39 years old. Her mother’s sister also had a thyroid nodule removed at the age of 15 years and ovarian surgery when she was approximately 30 years old. Additionally, the patient’s maternal grandmother had partial removal of the thyroid gland when she was 20 years old and is currently undergoing treatment for Graves’ disease. As a result of DICER1 mutation analysis, c.4509C> G (p.Y1503X) was identified as the heterozygous allele for the patient, her mother, and maternal grandmother.

Discussion & conclusion: We speculated that the novel DICER1 mutation was pathogenic because of the nonsense mutation, and because the mutation positive patients demonstrated a history of thyroid nodules. Although DICER1 mutation patients have reported familial thyroid differentiated cancer, there is no report of poorly differentiated thyroid carcinoma, suggesting that an additional somatic mutation might be responsible for neoplastic transformation. DICER1 mutation analysis is considered to be very important in the treatment protocol and for the management of complications in childhood onset MNG.

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