Snabboon Thiti, Plengpanich Wanee, Buranasupkajorn Patinat, Khwanjaipanich Ratchada, Vasinanukorn Padiporn, Suwanwalaikorn Sompongse, Khovidhunkit Weerapan, Shotelersuk Vorasuk
Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Horm Res. 2008;69(1):60-4. doi: 10.1159/000111797. Epub 2007 Dec 4.
POU1F1 is a pituitary transcription factor that plays a pivotal role in pituitary development and expression of the GH, PRL and TSH beta genes. Therefore, abnormalities of the POU1F1 gene are known to be responsible for a phenotype causing combined pituitary hormone deficiency (CPHD) involving growth hormone, prolactin and thyrotropin.
We described an 18-year-old Thai man, from a consanguineous family, who presented with short stature and cognitive deficit. He underwent endocrinological and molecular investigations.
Hormonal studies showed that the patient had GH deficiency and secondary hypothyroidism, consistent with CPHD. Direct DNA sequencing revealed a novel homozygous mutation at the splice site of exon 4, IVS4+1G>A. It is the first splice site mutation in the POU1F1 gene described to date. Of the 7 other family members studied for this mutation by restriction enzyme digestions, 5 were heterozygous. They were all unaffected, suggesting a recessive pattern of inheritance.
We described a novel POU1F1 splice site mutation, IVS4+1G>A, the first of its kind, in a Thai patient with CPHD. Recessive inheritance is suggested. We also noted preventable morbidities which resulted from delay in diagnosis of concomitant pituitary hormone defects in newborns suspected of CPHD.
POU1F1是一种垂体转录因子，在垂体发育以及生长激素（GH）、催乳素（PRL）和促甲状腺激素β（TSHβ）基因的表达中起关键作用。因此，已知POU1F1基因异常会导致一种引起包括生长激素、催乳素和促甲状腺激素在内的联合垂体激素缺乏（CPHD）的表型。
我们描述了一名来自近亲家庭的18岁泰国男性，他表现为身材矮小和认知缺陷。他接受了内分泌学和分子学检查。
激素研究表明该患者存在生长激素缺乏和继发性甲状腺功能减退，符合联合垂体激素缺乏症。直接DNA测序显示在第4外显子的剪接位点存在一个新的纯合突变，IVS4+1G>A。这是迄今为止所描述的POU1F1基因中的首个剪接位点突变。通过限制性酶切对该突变进行研究的其他7名家庭成员中，5名是杂合子。他们均未受影响，提示为隐性遗传模式。
我们在一名患有联合垂体激素缺乏症的泰国患者中描述了一种新的POU1F1剪接位点突变IVS4+1G>A，这是首例此类突变。提示为隐性遗传。我们还注意到在疑似患有联合垂体激素缺乏症的新生儿中，由于对伴随的垂体激素缺陷诊断延迟而导致的可预防的发病率。
