Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the PIT1/POU1F1 gene
Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the PIT1/POU1F1 gene
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DOI：
10.1210/jc.86.4.1545
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发表时间：
2001-04-01
影响因子：
5.8
通讯作者：
Jansen, M
中科院分区：
文献类型：
--
作者：
Hendriks-Stegeman, BI;Augustijn, KD;Jansen, M
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 POU-specific domain (W193R), which causes a 500-fold reduction in the ability to bind to DNA and activate transcription.
