Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery
Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery
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DOI：
10.20945/2359-3997000000139
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发表时间：
2019-04-01
期刊：
影响因子：
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通讯作者：
Mendonça, Berenice B.
中科院分区：
文献类型：
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作者：
Correa, Fernanda A.;Nakaguma, Marilena;Mendonça, Berenice B.
由PROP1突变引起的合并垂体激素缺乏症（CPHD）患者的首次描述是在20年前。在这里，我们更新了PROP1突变患者的临床和遗传特征，并总结了在圣保罗大学临床医院随访的14例具有7种不同致病性PROP1突变的患者的表型。除了GH、TSH、PRL和促性腺激素缺乏外，一些患者还会出现晚期ACTH缺乏。因此，需要对PROP1突变患者进行永久性监测。磁共振显示垂体柄正常，后叶位置正常。PROP1突变患者的前叶通常发育不全，但也可能正常甚至增大。双等位基因PROP1突变是目前世界范围内公认的CPHD最常见的遗传原因。PROP1缺陷在近亲父母和家族病例的后代中更常见，但也发生在散发病例中，特别是在PROP1突变流行率相对较高的国家。我们根据美国医学遗传学与基因组学学院和分子病理学协会（ACMG-AMP）指南对迄今为止报道的所有PROP1变异进行了分类：29种是致病的，2种可能是致病的，2种意义未知。自20年前首次描述以来，观察到PROP1突变患者表型的扩展：垂体前叶大小可变，不同的致病突变和ACTH缺乏的晚期发展。PROP1突变是常染色体隐性CPHD伴垂体后叶病变的最常见原因。
The first description of patients with combined pituitary hormone deficiencies (CPHD) caused by PROP1 mutations was made 20 years ago. Here we updated the clinical and genetic characteristics of patients with PROP1 mutations and summarized the phenotypes of 14 patients with 7 different pathogenic PROP1 mutations followed at the Hospital das Clinicas of the University of Sao Paulo. In addition to deficiencies in GH, TSH, PRL and gonadotropins some patients develop late ACTH deficiency. Therefore, patients with PROP1 mutations require permanent surveillance. On magnetic resonance imaging, the pituitary stalk is normal, and the posterior lobe is in the normal position. The anterior lobe in patients with PROP1 mutations is usually hypoplastic but may be normal or even enlarged. Bi-allelic PROP1 mutations are currently the most frequently recognized genetic cause of CPHD worldwide. PROP1 defects occur more frequently among offspring of consanguineous parents and familial cases, but they also occur in sporadic cases, especially in countries in which the prevalence of PROP1 mutations is relatively high. We classified all reported PROP1 variants described to date according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines: 29 were pathogenic, 2 were likely pathogenic, and 2 were of unknown significance. An expansion of the phenotype of patients with PROP1 mutations was observed since the first description 20 years ago: variable anterior pituitary size, different pathogenic mutations, and late development of ACTH deficiency. PROP1 mutations are the most common cause of autosomal recessive CPHD with a topic posterior pituitary lobe.