Faculty Collaboration Database

Congenital isolated adrenocorticotropin deficiency: an underestimated cause of neonatal death, explained by TPIT gene mutations. J Clin Endocrinol Metab 2005 Mar;90(3):1323-31

Date

12/23/2004

Pubmed ID

15613420

DOI

10.1210/jc.2004-1300

Scopus ID

2-s2.0-20144388457 (requires institutional sign-in at Scopus site)   119 Citations

Abstract

Tpit is a T box transcription factor important for terminal differentiation of pituitary proopiomelanocortin-expressing cells. We demonstrated that human and mouse mutations of the TPIT gene cause a neonatal-onset form of congenital isolated ACTH deficiency (IAD). In the absence of glucocorticoid replacement, IAD can lead to neonatal death by acute adrenal insufficiency. This clinical entity was not previously well characterized because of the small number of published cases. Since identification of the first TPIT mutations, we have enlarged our series of neonatal IAD patients to 27 patients from 21 unrelated families. We found TPIT mutations in 17 of 27 patients. We identified 10 different TPIT mutations, with one mutation found in five unrelated families. All patients appeared to be homozygous or compound heterozygous for TPIT mutations, and their unaffected parents are heterozygous carriers, confirming a recessive mode of transmission. We compared the clinical and biological phenotype of the 17 IAD patients carrying a TPIT mutation with the 10 IAD patients with normal TPIT-coding sequences. This series of neonatal IAD patients revealed a highly homogeneous clinical presentation, suggesting that this disease may be an underestimated cause of neonatal death. Identification of TPIT gene mutations as the principal molecular cause of neonatal IAD permits prenatal diagnosis for families at risk for the purpose of early glucocorticoid replacement therapy.

Author List

Vallette-Kasic S, Brue T, Pulichino AM, Gueydan M, Barlier A, David M, Nicolino M, Malpuech G, Déchelotte P, Deal C, Van Vliet G, De Vroede M, Riepe FG, Partsch CJ, Sippell WG, Berberoglu M, Atasay B, de Zegher F, Beckers D, Kyllo J, Donohoue P, Fassnacht M, Hahner S, Allolio B, Noordam C, Dunkel L, Hero M, Pigeon B, Weill J, Yigit S, Brauner R, Heinrich JJ, Cummings E, Riddell C, Enjalbert A, Drouin J

MESH terms used to index this publication - Major topics in bold

Adolescent
Adrenocorticotropic Hormone
Adult
Age of Onset
Cause of Death
Child
Female
Genes, Recessive
Homeodomain Proteins
Humans
Infant, Newborn
Infant, Newborn, Diseases
Male
Mutation
Pedigree
T-Box Domain Proteins
Transcription Factors