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- Title
Combined Pituitary Hormone Deficiency Caused by Compound Heterozygosity for Two Novel Mutations in the POU Domain of the PIT1/POU1F1 Gene.
- Authors
HENDRIKS-STEGEMAN, BRENDA I.; AUGUSTIJN, KEVIN D.; BAKKER, BERT; HOLTHUIZEN, PIETERNELLA; VAN DER VLIET, PETER C.; JANSEN, MAARTEN
- Abstract
The POU homeodomain containing transcriptional activator POU1F1, formerly called Pit1 or GHF-1, is required for the embryological determination and postnatal secretory function of the GH-, PRL-, and TSH-producing cells in the anterior pituitary. Several mutations in the gene encoding POU1F1 have been described, resulting in a syndrome of combined pituitary hormone deficiency involving these three hormones. Most of the patients with this phenotype have either a dominant negative mutation in codon 271 (R271W) or are homozygous for a recessive mutation in the POU1F1 gene; to date only one case has been reported with compound heterozygosity for two point mutations. Here, we describe a boy with severe deficiencies of GH, PRL, and TSH who had compound heterozygosity for two novel point mutations in the POU1F1 gene: a 1-bp deletion frameshift mutation (747delA), the first one described to date in this gene, which leads to a nonfunctional truncated protein lacking the entire DNA recognition helix of the POU homeodomain, and a missense mutation in the C-terminal end of the fourth a-helix of the POUspecific domain (W193R),which causes a 500-fold reduction in the ability to bind to DNA and activate transcription.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2001, Vol 86, Issue 4, p1545
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jcem.86.4.7371