Vieira Teresa C, da Silva Magnus R Dias, Abucham Julio
Division of Endocrinology, Department of Medicine, Universidade Federal de São Paulo-UNIFESP, São Paulo, Brazil.
Endocrine. 2006 Dec;30(3):365-9. doi: 10.1007/s12020-006-0015-2.
Combined pituitary hormone deficiency (CPHD) corresponds to impaired production of growth hormone (GH) and other anterior pituitary hormones. The genetic form of CPHD may result from mutations in pituitary transcription factor genes, and PROP1 is the most commonly mutated gene in these cases. Patients with PROP1 mutations may have variable CPHD phenotypes but, because they are usually treated in childhood, the wide phenotypic variability caused by these mutations may not be thoroughly appreciated.
Clinical follow-up and molecular analysis of PROP1 in two adult brothers with CPHD, born from consanguineous parents, and not treated until late adulthood.
The homozygous R120C mutation was identified in the brothers. Their clinical follow-up showed a wide phenotypic variability: hypogonadism was severe and prevented pubertal development in both, but their final heights were remarkably different, pointing to different degrees in severity of GH/TSH deficiencies; cortisol deficiency developed late in both, but at least 10 yr apart.
The lack of treatment in childhood and adolescence allowed the appreciation of the entire natural history of the CPHD caused by the R120C mutation, and it revealed a remarkable phenotypic variability even in siblings with a very similar genetic background.
联合垂体激素缺乏症（CPHD）表现为生长激素（GH）及其他垂体前叶激素分泌受损。CPHD的遗传形式可能源于垂体转录因子基因突变，其中PROP1是此类病例中最常发生突变的基因。携带PROP1突变的患者可能具有多种CPHD表型，但由于他们通常在儿童期接受治疗，这些突变所导致的广泛表型变异性可能未得到充分认识。
对两名成年兄弟进行临床随访，并对其PROP1进行分子分析。这两名兄弟患有CPHD，父母为近亲结婚，直至成年晚期才开始治疗。
在这两名兄弟中鉴定出纯合的R120C突变。他们的临床随访显示出广泛的表型变异性：性腺功能减退均很严重，均阻止了青春期发育，但他们的最终身高显著不同，表明GH/TSH缺乏的严重程度不同；两人的皮质醇缺乏均在后期出现，但相隔至少10年。
儿童期和青春期未接受治疗，使得我们能够了解由R120C突变引起的CPHD的整个自然病程，并揭示出即使在遗传背景非常相似的兄弟姐妹中也存在显著的表型变异性。
