Clinical and genetic features of a family with multinodular goiter harboring a DICER1 c.2035 A >G variant.

Objective: To investigate the clinical characteristics and causal gene mutations in a family with multinodular goiter (MNG).

Methods: A proband and eight family members were enrolled in the study. All participants underwent clinical examination and laboratory tests. Whole exome sequencing was performed on selected individuals. Peripheral venous samples were collected from the subjects, and genomic DNA was extracted. DNA library construction and exome capture were performed on an Illumina HiSeq 4000 platform. The data were analyzed, and Sanger sequencing was used to confirm that there was a variant in the original DNA and to evaluate the inheritance pattern in the family members. MNG tissue obtained from two family members was sequenced by whole exome sequencing.

Results: The proband and four family members were diagnosed with MNG and had undergone thyroidectomy, one of whom was pathologically diagnosed with papillary thyroid microcarcinoma. Thyroid function tests of all family members were normal. Exome sequence analysis identified a heterozygous variant, NM_177438.3:c.2035 A > G (NP_803187.1:p.Ile679Val), in exon 12 of the DICER1 gene in the proband and six family members. The variant was consistent with an autosomal dominant inheritance pattern. However, somatic DICER1 mutation was not detected.

Conclusions: The germline variant NM_177438.3:c.2035 A > G (NP_803187.1:p.Ile679Val) in DICER1 gene was first reported in individuals affected with DICER1-related conditions. It is important to take a detailed family history of patients with MNG. Genetic analysis can help diagnose DICER1 syndrome.