Short Stature Due to a Novel Compound Heterozygous Mutation of the POU1F1 Gene

We describe a 19-month-old male with GH deficiency, central hypothyroidism, and hypoprolactinemia due to a novel mutation of POU1F1. The patient presented with short stature and a compound heterozygous mutation of POU1F1: the pathogenic nonsense variant was inherited from his mother [c.514C > T (p.Arg172)] and a variant of unknown significance from his father [c.182G > T (p.Gly61Val)]. He had a recumbent length of 69 cm (Z score -5.27) and a weight of 7.94 kg (Z score -3.09) at 19 months. Further evaluation showed free T4 0.8 ng/dL (10.3 pmol/L) [reference range: 0.88-4.8 ng/dL (11.3-61.8 pmol/L)], TSH 3.270 µIU/mL (reference range: 0.82-5.91 µIU/mL), IGF binding protein 3 407 µg/L (reference range: 1289 -3634 µg/L), and prolactin 3.1 ng/mL [(7.75 nmol/L) (reference range: 5.3-28.9 ng/mL) (13.5-72.3 nmol/L)]. Levothyroxine, 3.1 µg/kg/day was started. A GH stimulation test using clonidine showed a peak GH level of 0.7 ng/mL (0.7 µg/L) [reference range: ≥ 10 ng/mL (≥ 10 µg/L)]. Magnetic resonance imaging of the brain showed anterior pituitary hypoplasia. He was started on GH 0.17 mg/kg/week with good response. To the best of our knowledge, the c.182G > T (p. Gly61Val) variant in POU1F1 is likely pathogenic, contributing to the pituitary hormone deficiencies in this child.