title: Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene.
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 alpha-helix of the POU-specific domain (W193R),which causes a 500-fold reduction in the ability to bind to DNA and activate transcription.
authors: Department of Pediatric Endocrinology, University Medical Center, 3508 AB Utrecht, The Netherlands.
authors: B I
authors: BI
authors: Hendriks-Stegeman
authors: K D
authors: KD
authors: Augustijn
authors: B
authors: B
authors: Bakker
authors: P
authors: P
authors: Holthuizen
authors: P C
authors: PC
authors: van der Vliet
authors: M
authors: M
authors: Jansen
mesh_terms: D002460:Cell Line; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D010907:Pituitary Hormones / Q000172:deficiency*; D017434:Protein Structure, Tertiary; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D010907:Pituitary Hormones; D014157:Transcription Factors