1. Congenital Isolated Adrenocorticotropin Deficiency: An Underestimated Cause of Neonatal Death, Explained byTPITGene Mutations
- Author
-
Carl-Joachim Partsch, Pierre Déchelotte, Thierry Brue, Begüm Atasay, Dominique Beckers, Anne Barlier, Leo Dunkel, Patricia A. Donohoue, Monique De Vroede, Jacques Weill, M. Gueydan, Georges Malpuech, Marc Nicolino, Jennifer H. Kyllo, Christie Riddell, B. Pigeon, Bruno Allolio, C. Noordam, Cheri Deal, Juan J. Heinrich, Sophie Vallette-Kasic, Anne-Marie Pulichino, Michel David, Felix G. Riepe, Jacques Drouin, Raja Brauner, Merih Berberoğlu, Matti Hero, Stefanie Hahner, Martin Fassnacht, Guy Van Vliet, Alain Enjalbert, Francis de Zegher, Elizabeth A. Cummings, Wolfgang G. Sippell, Sevket Yigit, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de pédiatrie, Interactions cellulaires neuroendocriniennes (ICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), and Gautron, Conception
- Subjects
Adult ,Male ,medicine.medical_specialty ,Health aging / healthy living [IGMD 5] ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Genes, Recessive ,030209 endocrinology & metabolism ,Prenatal diagnosis ,Adrenocorticotropic hormone ,Biology ,Gene mutation ,Compound heterozygosity ,medicine.disease_cause ,Biochemistry ,Infant, Newborn, Diseases ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Adrenocorticotropic Hormone ,Cause of Death ,Internal medicine ,medicine ,Adrenal insufficiency ,Humans ,Age of Onset ,Child ,030304 developmental biology ,Cause of death ,Homeodomain Proteins ,0303 health sciences ,Mutation ,Endocrinology and reproduction [UMCN 5.2] ,Biochemistry (medical) ,Infant, Newborn ,medicine.disease ,Pedigree ,3. Good health ,Mitochondrial medicine [IGMD 8] ,Female ,T-Box Domain Proteins ,Adrenocorticotropic hormone deficiency ,Transcription Factors - Abstract
Item does not contain fulltext 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.
- Published
- 2005
- Full Text
- View/download PDF