Molecular genetic study on sex determination, differentiation and sexual differentiation anomaly.

性别决定、分化及性分化异常的分子遗传学研究。

• 批准号: 08671858
• 负责人: HOSHI Nobuhiko
• 金额: $ 1.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671858/
• 关键词: Sex differentation anomaly; Sex determination; Sex differentiation; SRY; TDF; Cytogenetics and molecular genetics; Mosaicisms; Chimeras; 細胞・分化遺伝子; SPY; 分子遺伝学; 細胞遺伝; 双胎; 多胎妊娠

In a total of 40 individuals from 19 cases (25 samples from 10 cases of phenotypic females including 3 Turner's syndrome, and 15 samples from 9 cases of phenotypic males), which was presumed as sex differentiation anomaly by clinical and cytogenetic findings, peripheral blood, cord blood, skin, gonad, bucal cells, born marrow, amniotic fluid and placental chorionic villi were examined by FISGH,Southern blot hybridization, PCR and direct DNA sequencing for X (3 loci) and Y chromosomes (27 loci). Marker chromosomes were demonstrated that 2 cases were derived from X and 7 were derived from Y by using G,Q banding and FISH.Among the samples analyzrd, a total of 15 ceses including of these 7 cases from Y,3 cases of 45, X/46, XY,2 cases of gonadoblastoma (XX,XY), 2 cases of ambiguous external genitalia (XX,XY) and 1 cases 0f small Y,a case of ovotestis with 46, XX (peripheral blood and both right and left gonads), and XX male with hypospadias and cryptorchild testis (petipheral blood) were found any Y contents. A case of monozygotic twins of discordant sex both with 47, X,idic (Yp)*2/45, X/46, X,idic (Yp) mosaicism was demonstrated to lack from Yq11.2 to Yq terminal. A case of dizygotic twins of discordant sex was revealed to be blood chimerism. In 2 cases of 46, X,+mar, the markers were demonstrated derived from a Y chromosome including P terminal to q11.23 and paracentric inversion in the remained Y long arm, and i (Y) (p10) individually. Five cases of Phenotypic female with 46, X,+mar, mosaicism of 45, X cell line were found in several tissue including gonads. No deletion and mutation were demonstrated in SRY positive cases.The present report illustrates the importance of mosaicism in relation to sex chromosome, and FISH and molecular techniques as a complement to cytogenetic method for accurate identification and characterization of chromosome rearrangements in "sex determination"and "sex differentation".

总共40个人从19例(25个样本10例女性表型包括3特纳氏综合征,和15 9例样本表型男性),假定的性分化异常的临床和细胞遗传学的发现,外周血、脐带血,皮肤,性腺,bucal细胞,骨髓出生,羊水、胎盘绒毛膜绒毛被FISGH检查,印迹杂交,PCR和DNA直接测序X(3位点)和Y染色体(27个位点)。标记染色体通过G带、Q带和FISH分析证实2例来自X， 7例来自Y。在分析的样本中，共15例，其中7例来自Y，3例来自45、X/46、XY，2例性腺母细胞瘤（XX、XY）， 2例外生殖器模糊（XX、XY）和1例小Y， 1例卵睾46、XX（外周血及左右性腺），以及XX例尿道下裂和隐睾（阴蒂血），均发现有Y含量。1例性别不一致的同卵双胞胎，从Yq11.2到Yq端均缺乏47，X,idic (Yp)*2/45, X/46， X,idic （Yp）嵌合。一例性别不一致的异卵双胞胎被发现是血液嵌合。在2例46、X、+mar中，标记分别来自一条Y染色体，包括P末端至q11.23和剩余Y长臂的顺中心倒置，分别为i (Y) （p10）。5例表型雌性在生殖腺等多个组织中发现46、X、+mar、45、X细胞系嵌合。在SRY阳性病例中未发现缺失和突变。本报告阐明了镶嵌现象在性染色体方面的重要性，以及FISH和分子技术作为细胞遗传学方法的补充，在“性别决定”和“性别分化”中准确识别和表征染色体重排。

项目成果

Okuyama, K., Hoshi, N., Fujimoto, S: "Prenatal diagnosis in genetic disorders." Obstet. Gynecol.64. 1689-1694 (1997)

Okuyama, K.、Hoshi, N.、Fujimoto, S：“遗传性疾病的产前诊断。”

Nobuhiko, Hoshi: "Seminoma in a postmenopausal woman who demonstrated a Y ; 15 translocation in peripheralbloodlymphocytes,and a t (Y ; 15) /45, X Turner mosaic pattern in skin fibroblasts." J.Med.Genet.35(in press). (1998)

Nobuhiko, Hoshi：“绝经后妇女的精原细胞瘤，外周血淋巴细胞中表现出 Y ; 15 易位，皮肤成纤维细胞中表现出 t (Y ; 15) /45, X 特纳镶嵌图案。”

奥山 和彦: "わが教室における胎児診断と治療" 産婦人科治療. 74. 76-83 (1997)

奥山和彦：“我的课堂上的胎儿诊断和治疗”妇产科治疗74。76-83（1997）。

藤本 俊郎: "外陰の奇形" 産婦人科の実際. 46. 695-709 (1997)

Toshiro Fujimoto：“外阴畸形”妇产科实践 46. 695-709 (1997)。

奥山 和彦: "出生前診断における母体血清マーカーの現時点での評価" 産婦人科の世界. 49. 77-84 (1997)

Kazuhiko Okuyama：“产前诊断中母体血清标志物的当前评估”《妇产科世界》49. 77-84 (1997)。