Laboratoire Center National Of La Recherche Scientifique Unite Mixte Of Recherche 6231

Marseille, France

Laboratoire Center National Of La Recherche Scientifique Unite Mixte Of Recherche 6231

Marseille, France

Time filter

Source Type

Couture C.,Institute Of Recherches Cliniques Of Montreal | Saveanu A.,Laboratoire Center National Of La Recherche Scientifique Unite Mixte Of Recherche 6231 | Saveanu A.,Center Hospitalier University Conception | Barlier A.,Laboratoire Center National Of La Recherche Scientifique Unite Mixte Of Recherche 6231 | And 13 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Congenital isolated ACTH deficiency (IAD) is a rare disease characterized by low plasma ACTHandcortisol levelsandpreservation of all other pituitary hormones. This conditionwaspoorly defined beforeweidentified TPIT, a T-box transcription factor with a specific role in differentiation of the corticotroph lineage in mice and humans, as its principal molecular cause. Objective: We have enlarged our series of IAD patients to better characterize the phenotype and the genotype of this rare disease. Design: Each exon of the TPIT gene was amplified and sequenced in IAD patients without any identified cause. A functional analysis of each new TPIT mutation was performed. Results: We described the largest series of 91 IAD patients and identified three distinct groups: neonatal onset complete or partial IAD or late onset IAD. We did not identify any TPIT mutation in patients with partial or late-onset IAD. However, we found a TPIT mutation in 65% of patients with neonatal-onset complete IAD. These patients arehomozygousorcompoundheterozygous for TPIT mutations, and their parents are healthy heterozygous carriers. We identified nine new mutations: four missense, one one-nucleotide deletion, three splice-site mutations, and one large deletion. TPIT mutations lead to loss of function by different mechanisms, such as non-sensemediated mRNA decay, abnormal mRNA splicing, loss of TPIT DNA binding or protein-protein interaction defects. Conclusion: TPIT mutations are responsible for two thirds of neonatal-onset complete IAD but can not be detected in partial or late-onset IAD. Copyright © 2012 by The Endocrine Society.

Loading Laboratoire Center National Of La Recherche Scientifique Unite Mixte Of Recherche 6231 collaborators
Loading Laboratoire Center National Of La Recherche Scientifique Unite Mixte Of Recherche 6231 collaborators