Objective: To identify the genetic defect in a neonate presented with prolonged jaundice and central hypothyroidism.
Design: Central hypothyroidism was detected in a neonate initially examined for prolonged jaundice, and levothyroxine therapy was initiated. Direct sequencing of the Prop1 gene was carried out and pituitary function and morphology were evaluated using hormonal testing and magnetic resonance imaging (MRI) respectively.
Methods: Dynamic hormonal testing was carried out using established methodologies. Hormones were determined by RIA or chemiluminescence immunoassays. Genomic analysis of the Prop1 gene was performed by direct sequencing. MRI protocol: sagittal spin echo T2-weighted scans 2500/90 (TR/TE), plain and contrast-enhanced sagittal and coronal spin echo T1-weighted scans 500/20 (TR/TE).
Results: Low thyroid hormones (coupled with lack of TSH rise), low GH, normal cortisol and normal prolactin values were detected. Direct sequencing revealed the presence of two mutations in the Prop1 gene: GA296del and Q83X. The Q83X was further confirmed by PvuII restriction digestion and represented a novel Prop1 gene mutation, which was not detected in 100 controls tested. Pituitary enlargement was detected, with respect to normal-for-age controls.
Conclusions: (i) The Q83X mutation extends the spectrum of Prop1 gene mutations; (ii) central hypothyroidism in a neonate might constitute the initial sign of Prop1 gene defect; (iii) the patient is the youngest individual with Prop1 gene defect and pituitary enlargement presented to date; and (iv) early detection of Prop1 gene mutations facilitates genetic counseling and ensures prompt management of the anticipated hormonal insufficiencies.