Tajima Toshihiro, Sasaki Satoshi, Tanaka Yayoi, Kusunoki Hiroyuki, Nagashima Testuro, Nonomura Katsuya, Fujieda Kenji
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan.
Horm Res. 2003;60(6):302-5. doi: 10.1159/000074249.
Frasier syndrome is characterized by progressive glomerulopathy due to nonspecific focal and segmental glomerulosclerosis (FSGS), 46,XY sex reversal and the development of gonadoblastoma from dysgenetic gonads. Donor splice site heterozygous mutations in intron 9 of the Wilms' tumor gene (WT1) cause this disease. We investigated whether WT1 mutations showed clinical heterogeneity.
A 6-year-old phenotypic boy was diagnosed as having FSGS. His karyotype was 46,XY. Gonadotropin-releasing hormone and human chorionic gonadotropin stimulation tests revealed normal luteinizing hormone, follicle-stimulating hormone and testosterone responses. The other patient was a 7-year-old 46,XY female with FSGS. Prophylactic gonadectomy was performed and gonadoblastoma was found. By polymerase chain reaction and direct sequencing, WT1 was analyzed in these patients.
Both patients had IVS9 + 5G-->A in intron 9 of the WT1. Our study indicates a normal 46,XY phenotypic male patient with FSGS. The phenotypic variations of the WT1 splice site mutations are further expanded.
弗雷泽综合征的特征是由于非特异性局灶节段性肾小球硬化（FSGS）导致进行性肾小球病、46，XY性反转以及发育不全的性腺发生性腺母细胞瘤。肾母细胞瘤基因（WT1）第9内含子中的供体剪接位点杂合突变导致该病。我们研究了WT1突变是否表现出临床异质性。
一名6岁表型为男性的患儿被诊断为FSGS。其核型为46，XY。促性腺激素释放激素和人绒毛膜促性腺激素刺激试验显示黄体生成素、卵泡刺激素和睾酮反应正常。另一名患者是一名7岁的46，XY女性，患有FSGS。进行了预防性性腺切除术，发现了性腺母细胞瘤。通过聚合酶链反应和直接测序对这些患者的WT1进行了分析。
两名患者的WT1第9内含子均存在IVS9 + 5G→A。我们的研究表明，一名患有FSGS的46，XY表型正常男性患者。WT1剪接位点突变的表型变异进一步扩大。
