Department of Medical Genetics, Medical School, University of Athens, Aghia Sophia Children's Hospital, Athens, Greece.
Hormones (Athens). 2012 Jul-Sep;11(3):361-7. doi: 10.14310/horm.2002.1366.
Frasier syndrome (FS) phenotype in 46,XY patients usually consists of female external genitalia, gonadal dysgenesis, high risk of gonadoblastoma and the development of end stage renal failure usually in the second decade of life. FS is caused by heterozygous de novo intronic splice site mutations of the Wilms' tumor suppressor gene 1 (WT1), although a few cases with typical exonic WT1 Denys-Drash mutations that resemble an FS phenotype have been described. The aim of this study was to present further data on the spectrum of FS phenotypes through the evaluation of a 29-year-old patient with a predominantly male phenotype and coexistence of Sertoli cell tumor and gonadoblastoma.
Genetic analysis using standard methods for DNA sequencing confirmed FS due to a WT1 gene mutation, IVS9+4C>T.
This very rare case illustrates the natural course of FS over many years due to the neglect by the patient to address his need for follow-up, while adding further data on the spectrum of FS phenotypes associated with IVS9+4 C>T mutations. The coexistence of the rare Sertoli cell tumor and gonadoblastoma emphasizes that early clinical recognition and molecular identification facilitates appropriate patient management, especially with respect to the high risk of gonadal malignancy.
46,XY 患者的弗雷泽综合征（FS）表型通常包括女性外生殖器、性腺发育不良、罹患性腺母细胞瘤的风险较高，并且通常在生命的第二个十年发展为终末期肾病。FS 是由 Wilms' 肿瘤抑制基因 1（WT1）的杂合新生内含子剪接位点突变引起的，尽管已经描述了少数具有类似于 FS 表型的典型外显子 WT1 Denys-Drash 突变的病例。本研究的目的是通过评估一名 29 岁主要表现为男性表型且并存 Sertoli 细胞瘤和性腺母细胞瘤的患者，进一步展示 FS 表型谱的数据。
使用标准的 DNA 测序方法进行的遗传分析证实了 FS 是由于 WT1 基因突变，即 IVS9+4C>T 引起的。
这个非常罕见的病例说明了 FS 多年来的自然病程，因为患者忽视了他对随访的需求，同时增加了与 IVS9+4 C>T 突变相关的 FS 表型谱的进一步数据。罕见的 Sertoli 细胞瘤和性腺母细胞瘤并存强调了早期临床识别和分子鉴定有助于对患者进行适当的管理，特别是考虑到性腺恶性肿瘤的高风险。
