Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery

Author(s)

Correa, Fernanda A. ^[1] ; Nakaguma, Marilena ^[1] ; Madeira, Joao L. O. ^[1] ; Nishi, Mirian Y. ^[1] ; Abrao, Milena G. ^[1] ; Jorge, Alexander A. L. ^[2] ; Carvalho, Luciani R. ^[1] ; Arnhold, Ivo J. P. ^[1] ; Mendonca, Berenice B. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med, Hosp Clin, Discipline Endocrinol, Unidade Endocrinol Desenvolvimento, Lab Hormenios, Av Dr Eneas de Carvalho Aguiar 255, BR-05403000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Fac Med, Hosp Clin, Discipline Endocrinol, Unidade Endocrinol Genet, Lab Endocrinol Celular &, Sao Paulo, SP - Brazil

• Document type: Review article
• Source: ARCHIVES OF ENDOCRINOLOGY METABOLISM; v. 63, n. 2, p. 167-174, MAR-APR 2019.
• Web of Science Citations: 0

Abstract

The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clinicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe. (AU)

• FAPESP's process: 13/03236-5 - New approaches and methodologies in molecular-genetic studies of growth and pubertal development disorders
• Grantee: Alexander Augusto de Lima Jorge
• Support type: Research Projects - Thematic Grants