BACKGROUND/AIMS: Recent studies have pointed to the correlation between FOXE1 polyalanine tract (FOXE1-polyAla) length polymorphism and genetic susceptibility to thyroid dysgenesis causing congenital hypothyroidism. The objective of this study was a first assessment of the role of FOXE1-polyAla expansion in the genetic background of thyroid hemiagenesis (TH). METHODS: The group studied consisted of 40 patients with TH, including 6 familial cases and a control group of 89 subjects with a normal thyroid. The polyAla tract and flanking sequence of FOXE1 was amplified using conventional PCR. Subsequently, capillary electrophoresis was performed to estimate the length of products. RESULTS: A short variant of FOXE1-polyAla, containing 12 alanines, was present in 5 control subjects (5.6%), but was not found in TH. The incidence of longer variants (≥16 codons) of FOXE1-polyAla was significantly higher in patients with the familial form of TH in comparison to those with sporadic TH (p = 0.003) and controls (p = 0.005). CONCLUSIONS: There is high polymorphic variability of FOXE1-polyAla in both groups. Shorter variants of FOXE1-polyAla are underrepresented in subjects with familial TH. Therefore, FOXE1-polyAla tract expansion may contribute to the molecular background of familial but not sporadic forms of TH. Further studies are still required to confirm such findings.
BACKGROUND/AIMS: Recent studies have pointed to the correlation between FOXE1polyalanine tract (FOXE1-polyAla) length polymorphism and genetic susceptibility to thyroid dysgenesis causing congenital hypothyroidism. The objective of this study was a first assessment of the role of FOXE1-polyAla expansion in the genetic background of thyroid hemiagenesis (TH). METHODS: The group studied consisted of 40 patients with TH, including 6 familial cases and a control group of 89 subjects with a normal thyroid. The polyAla tract and flanking sequence of FOXE1 was amplified using conventional PCR. Subsequently, capillary electrophoresis was performed to estimate the length of products. RESULTS: A short variant of FOXE1-polyAla, containing 12 alanines, was present in 5 control subjects (5.6%), but was not found in TH. The incidence of longer variants (≥16 codons) of FOXE1-polyAla was significantly higher in patients with the familial form of TH in comparison to those with sporadic TH (p = 0.003) and controls (p = 0.005). CONCLUSIONS: There is high polymorphic variability of FOXE1-polyAla in both groups. Shorter variants of FOXE1-polyAla are underrepresented in subjects with familial TH. Therefore, FOXE1-polyAla tract expansion may contribute to the molecular background of familial but not sporadic forms of TH. Further studies are still required to confirm such findings.
Authors: Joshua C Denny; Dana C Crawford; Marylyn D Ritchie; Suzette J Bielinski; Melissa A Basford; Yuki Bradford; High Seng Chai; Lisa Bastarache; Rebecca Zuvich; Peggy Peissig; David Carrell; Andrea H Ramirez; Jyotishman Pathak; Russell A Wilke; Luke Rasmussen; Xiaoming Wang; Jennifer A Pacheco; Abel N Kho; M Geoffrey Hayes; Noah Weston; Martha Matsumoto; Peter A Kopp; Katherine M Newton; Gail P Jarvik; Rongling Li; Teri A Manolio; Iftikhar J Kullo; Christopher G Chute; Rex L Chisholm; Eric B Larson; Catherine A McCarty; Daniel R Masys; Dan M Roden; Mariza de Andrade Journal: Am J Hum Genet Date: 2011-10-07 Impact factor: 11.025
Authors: Andrew C Lidral; Huan Liu; Steven A Bullard; Greg Bonde; Junichiro Machida; Axel Visel; Lina M Moreno Uribe; Xiao Li; Brad Amendt; Robert A Cornell Journal: Hum Mol Genet Date: 2015-02-04 Impact factor: 6.150