Chromosome 20p deletion, mutation and the FOXA2 gene

Chromosome 20p deletion, mutation and the FOXA2 gene. The FOXA2 gene is important in the development of the pituitary gland.

Development of the pituitary gland (PG) depends on a complex action of several transcription factors. Underdevelopment of the PG leads to growth delay, defects in metabolism, reproduction and other functions. The authors report a boy who was born with cleft lip and palate, preauricular pit on the right, short hands with tapering fingers, cryptorchidism and hypogonadism. Between ages 3 and 10 he was diagnosed with central hypothyroidism, central diabetes insipidus and central adrenal insufficiency. Hypoplastic PG and ectopic posterior pituitary were found upon magnetic resonance imaging. Further examination showed that his gallbladder was bilobed. Cytogenetic examination showed an 8.5 Mb deletion in 20p11.23p11.21 with the loss of 38 genes including the FOXA2 gene. This gene codes a protein which is one of transcription factors for the development of the PG. Treatment with sulfonurea produced a good response. Surprisingly intellectual development of this boy was normal. The authors analyzed 11 more cases with a deletion of this region of 20p involving the FOXA2 gene. Minimal deletion in this group was only 277 kb and the FOXA2 was the only lost gene. Growth hormone deficiency was found in almost all patients (only one 2-month old girl had a normal rate of pituitary hormones). PG in all examined persons was hypoplastic with ectopic posterior PG. At least 5 patients had abdominal heterotaxy or situs inversus. Four patients revealed different heart defects. The same abnormalities (low growth hormone, hypoplastic [or absent] anterior PG, ectopic posterior PG, heart defects and tendency to situs inversus were found in 6 patients with mutations in the FOXA2 gene. Three patients with mutations also had anal atresia which was not reported in patients with deletions. These data allow the consideration of the FOXA2 gene as a transcription factor which may play a key role in the development of the PG and the foregut derivatives.

Kaygusuz S.B. et al. “Dysgenesis and dysfunction of the pancreas and pituitary due to FOXA1 gene defects”. “J. Clin. Endocrinology & Metabolism” 2021, v. 106 (10), e4142-e4154.