BACKGROUND: PROP-1 gene mutations have been described in patients with combined pituitary hormone deficiencies (CPHD). METHODS: Clinical follow-up and molecular analysis of the PROP-1 gene were performed in 4 affected sisters of one consanguineous family, in whom 8 members had CPHD. RESULTS: The 4 sisters were homozygous for the same R120C mutation. Growth hormone and thyroid-stimulating hormone deficiencies were diagnosed concomitantly in all subjects, but at different ages (5.5-10.8 years). All 8 subjects exhibited complete gonadotropin deficiency with failure of spontaneous sexual maturation. Adrenocorticotropic hormone deficiency developed in only 2 sisters in the 3rd and 4th decades of life. CONCLUSIONS: The CPHD in this family, caused by an R120C mutation, was characterized by clinical phenotypic variability in terms of the severity of hormonal deficiencies and the time of their development. Identifying the mutation does not predict the clinical course. Therefore, continuous follow-up with repeated endocrine evaluations is mandatory to provide proper hormone substitution therapy. Copyright 2003 S. Karger AG, Basel
BACKGROUND:PROP-1 gene mutations have been described in patients with combined pituitary hormone deficiencies (CPHD). METHODS: Clinical follow-up and molecular analysis of the PROP-1 gene were performed in 4 affected sisters of one consanguineous family, in whom 8 members had CPHD. RESULTS: The 4 sisters were homozygous for the same R120C mutation. Growth hormone and thyroid-stimulating hormone deficiencies were diagnosed concomitantly in all subjects, but at different ages (5.5-10.8 years). All 8 subjects exhibited complete gonadotropin deficiency with failure of spontaneous sexual maturation. Adrenocorticotropic hormone deficiency developed in only 2 sisters in the 3rd and 4th decades of life. CONCLUSIONS: The CPHD in this family, caused by an R120C mutation, was characterized by clinical phenotypic variability in terms of the severity of hormonal deficiencies and the time of their development. Identifying the mutation does not predict the clinical course. Therefore, continuous follow-up with repeated endocrine evaluations is mandatory to provide proper hormone substitution therapy. Copyright 2003 S. Karger AG, Basel