ClinVar

In a proband who presented with papillary thyroid carcinoma (PTC) and nodal metastases (NMTC4; 616534) at the age of 57 years, Pereira et al. (2015) identified a heterozygous c.743C-G transversion in the FOXE1 gene, resulting in an ala248-to-gly (A248G) substitution. The variant was not identified in public databases. Three other family members also carried the variant: the proband's cousin was diagnosed with PTC at the age of 72 years, in addition to having other neoplasms; his consanguineous wife had an ovarian carcinoma; and the sister of the proband presented with PTC at the age of 57 and developed nodal metastases 2 years later. The proband's father was an obligate carrier but was deceased. The A248G mutation was also identified in an unrelated patient from a group of 80 unrelated persons with apparently sporadic NMTC. This patient developed PTC with nodal metastases at the age of 24 years. Functional studies showed increased cell growth and migration in the presence of the mutant protein. Pereira et al. (2015) also found the A248G mutation in 1 male patient among 80 unrelated Portuguese individuals with apparently sporadic NMTC. This patient had developed PTC with nodal metastases at the age of 24 years.