Kanemoto Katsuyoshi, Ishikura Kenji, Ariyasu Daisuke, Hamasaki Yuko, Hataya Hiroshi, Hasegawa Yukihiro, Ikeda Masahiro
Department of Nephrology, Tokyo Metropolitan Kiyose Children's Hospital, 1-3-1 Umezono, Kiyose, Tokyo, 204-8567, Japan.
Pediatr Nephrol. 2007 Mar;22(3):454-8. doi: 10.1007/s00467-006-0333-x. Epub 2006 Oct 24.
The Wilms' tumor suppressor gene (WT1) plays crucial roles in urogenital and gonadal development. Germline mutations of WT1 have been reported in patients with Denys-Drash syndrome (DDS) and Frasier syndrome (FS). Based on clinical overlaps reported to date, it has been suggested that these two syndromes should be considered as part of a spectrum of diseases caused by WT1 gene mutations, rather than as separate diseases. We report a new mutation in an intron 9 splice acceptor site (IVS -1G-->) in a Japanese 46,XY male patient with focal segmental glomerulosclerosis (FSGS) and bilateral cryptorchism. The clinical phenotype of this patient resembled FS without male pseudohermaphroditism. Interestingly, although the patient's right kidney was diagnosed with FSGS, his left kidney showed severe hypoplasia. There are no previous case reports of FSGS and renal hypoplasia in the same individual with a WT1 mutation. The findings for this case further suggest that the renal phenotype has various manifestations and is not always decided by the type of WT1 mutation. The possibility that the position of the WT1 mutation may influence the course of the nephropathy should be evaluated in a larger patient cohort.
威尔姆斯肿瘤抑制基因（WT1）在泌尿生殖系统和性腺发育中起关键作用。据报道，患有迪尼斯-德拉斯综合征（DDS）和弗雷泽综合征（FS）的患者存在WT1的种系突变。基于迄今报道的临床重叠情况，有人提出这两种综合征应被视为由WT1基因突变引起的一系列疾病的一部分，而非单独的疾病。我们报告了一名46，XY日本男性患者，其9号内含子剪接受体位点（IVS -1G-->)存在新突变，该患者患有局灶节段性肾小球硬化症（FSGS）和双侧隐睾症。该患者的临床表型类似FS，无男性假两性畸形。有趣的是，尽管患者的右肾被诊断为FSGS，但其左肾显示严重发育不全。此前尚无同一例携带WT1突变的个体同时患有FSGS和肾发育不全的病例报告。该病例的研究结果进一步表明，肾脏表型有多种表现形式，并不总是由WT1突变类型决定。WT1突变位置可能影响肾病病程这一可能性，应在更大的患者队列中进行评估。
