Does the Polymorphism in the Length of the Polyalanine Tract ofFOXE1Gene Influence the Risk of Thyroid Dysgenesis Occurrence?

Abstract

Background. Recent data have suggested that polymorphisms in the length of the polyalanine tract (polyA) of FOXE1 gene may act as a susceptibility factor for thyroid dysgenesis. The main purpose of this study was to investigate the influence of polyA of FOXE1 gene on the risk of thyroid dysgenesis. Method. A case-control study was conducted in a sample of 90 Brazilian patients with thyroid dysgenesis and 131 controls without family history of thyroid disease. Genomic DNA was isolated from peripheral blood samples and the genotype of each individual was determined by automated sequencing. Results. More than 90% of genotypes found in the group of patients with thyroid dysgenesis and in controls subjects were represented by sizes 14 and 16 polymorphisms in the following combinations: 14/14, 14/16, and 16/16. Genotypes 14/16 and 16/16 were more frequent in the control group, while genotype 14/14 was more frequent in the group of patients with thyroid dysgenesis. There was no difference between agenesis group and control group. Genotype 14/14 when compared to genotypes 14/16 and 16/16A showed an association with thyroid dysgenesis. Conclusion. PolyA of FOXE1 gene alters the risk of thyroid dysgenesis, which may explain in part the etiology of this disease.

Identification of Germline FOXE1 and Somatic MAPK Pathway Gene Alterations in Patients with Malignant Struma Ovarii, Cleft Palate and Thyroid Cancer

“…Regarding FOXE1 polyalanine tract expansions, FOXE1 16Ala has been associated with PTC [14,15]. In the present study, the 16-Ala allele (MAF gnomAD_NFE = 20-40%) [14,15,29,30] was detected in heterozygosity in the patient with MSO (F1, III.1), as well as in one family member with CP (F2, II.2) (Figure 1).…”

Disruption of the foxe1 gene in zebrafish reveals conserved functions in development of the craniofacial skeleton and the thyroid

“…Shorter PAS length in humans is associated with susceptibility to thyroid dysgenesis. However, it does not affect the binding of FOXE1 to the promoters of the TGFβ3 and MSX1 genes, which are important for skeletal development ( Carre et al, 2007 ; Venza et al, 2011 ; Pimentel et al, 2017 ). The absence of the PAS region in the zebrafish Foxe1 protein may partially explain why, up to now, no function of Foxe1 in thyroid development was found.…”

Genetics of congenital hypothyroidism: Modern concepts

“…In this context, the polymorphic nature of the polyalanine of the FOXE1 gene aroused great interest as a susceptibility factor. Several groups, including ours, have studied the relationship between the length of the FOXE1 polyalanine and the TD type, suggesting a role as a susceptibility factor in TDs 53–56 …”

“…Several groups, including ours, have studied the relationship between the length of the FOXE1 polyalanine and the TD type, suggesting a role as a susceptibility factor in TDs. 53 , 54 , 55 , 56 …”

“…Several groups, including ours, have studied the relationship between the length of the FOXE1 polyalanine and the TD type, suggesting a role as a susceptibility factor in TDs. [53][54][55][56] Furthermore, the high degree of inconsistency (92%) between monozygous twins and the sex difference with a higher feminine prevalence of CHTD are two arguments against classic Mendelian transmission. 57 The following somatic mechanisms could be involved: 1) early postzygotic somatic mutations, 2) specific tissue mutations or epimutations or 3) tissue-specific autosomal monoallelic expression of specific genes involved in the thyroid.…”