Irie Y, Tatsumi K, Ogawa M, Kamijo T, Preeyasombat C, Suprasongsin C, Amino N
Department of Laboratory Medicine, Osaka University Medical School, Japan.
Endocr J. 1995 Jun;42(3):351-4. doi: 10.1507/endocrj.42.351.
PIT1 abnormality is defined as a genetic abnormality in the PIT1 gene that encodes a pituitary specific transcription factor, Pit-1/GHF-1. PIT1 abnormality indicates combined deficiency of thyrotropin (TSH), growth hormone (GH) and prolactin (PRL), and has been reported in several cases. We studied the PIT1 gene in a patient with combined deficiency of TSH, GH and PRL. A novel mutation substituting a termination codon for Glutamate at 250th codon (E250X) was identified in the homozygous state in the patient. Both of the healthy parents harbored this mutation in the heterozygous state. This nonsense mutation results in complete loss of helix 3 of the POU homeodomain of Pit-1/GHF-1. As helix 3 of the homeodomain is involved directly in DNA binding, the mutant Pit-1/GHF-1 may lose the DNA binding activity of the POU homeodomain and lose its transcriptional activation. The E250X mutation is therefore considered to be the cause of the combined deficiency of TSH, GH and PRL in this patient.
PIT1异常被定义为编码垂体特异性转录因子Pit-1/GHF-1的PIT1基因中的一种基因异常。PIT1异常表明促甲状腺激素（TSH）、生长激素（GH）和催乳素（PRL）联合缺乏，并且已有多例相关报道。我们对一名TSH、GH和PRL联合缺乏的患者的PIT1基因进行了研究。在该患者中，发现了一种新的突变，即第250位密码子处的谷氨酸被终止密码子取代（E250X），且该突变处于纯合状态。患者的双亲健康，但均为该突变的杂合携带者。这种无义突变导致Pit-1/GHF-1的POU同源结构域的螺旋3完全缺失。由于同源结构域的螺旋3直接参与DNA结合，突变后的Pit-1/GHF-1可能会丧失POU同源结构域的DNA结合活性，进而失去其转录激活能力。因此，E250X突变被认为是该患者TSH、GH和PRL联合缺乏的原因。
