PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotrophdeficiency

Alterations of the gene encoding the pituitary transcription factor PROP1 w ere associated with congenital forms of multiple pituitary hormone deficien cies in several families. Among 23 patients with multiple pituitary hormone deficiencies screened for a PROP1 gene abnormality, nine belonging to eigh t unrelated families had homozygous PROP1 gene defects. All mutations were located in exon 2 and affected only two different sites: a homozygous AG de letion at codons 99/ 100/101 (n = 5); homozygous point mutations affecting codon 73: R73C (n = 2) or R73H (n = 1), and a R73C/R99X double-heterozygous mutation (n = 1). R73H and R99X were never described. All patients were bo rn to unaffected parents, and consanguinity was documented in two patients. They had complete GH, LH-FSH, and TSH deficiencies and normal basal levels of PRL. Delayed ACTH deficiency was diagnosed in four of nine patients. At magnetic resonance imaging the anterior pituitary was hypoplastic in seven patients and hyperplastic in two. This study found two novel mutations (R7 3H and R99X) and underlines the high incidence of PROP1 gene alterations in patients with multiple pituitary hormone deficiencies. A corticotroph defi ciency was frequently observed in association with GH, TSH, and gonadotropi n deficiencies and should be carefully sought during follow-up.