Study on Placental Sulfatase Deficiency ; Diagnosis, Treatment and Genetics

胎盘硫酸酯酶缺乏症的研究；

• 批准号: 01570940
• 负责人: YANAIHARA Takumi
• 金额: $ 1.41万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570940/
• 关键词: Placental sulfatase feficiency; Sulfatase; Placenta; Leukocytes; Ichthyosis; Estrogen excretion; 胎盤性サルファタ-ゼ欠損症; 胎盤性サルファタ-ゼ欠損性; エストロゲン排拙; エストロゲン排

Placental sulfatase deficiency(PSD)is a rare disorder with low estrogen production due to placental enzymatic deficiency- PSD is diagnosed by in vitro placental enzyme assay. In Japan, we have confirmed 65 cases of this disorder since 1979. In the present investigation, we have analysed the clinical data of 65 cases including the mode of delivery, family pedigree, birth weight of the infants, placental weight, developent of ichthyosis during the period of 1-3 months after birth. In addition, sulfatasse activity in peripheral blood leukocytes isolated from normal women and men, and the activity was compared to that from the PSD mothers and the infants. Deficiency of the sulfatase of the placenta obtained was confirmed by in vitro incubation with ^<14>C-DHA-Sulfate and the activity was expressed as the amounts of the free steroid. Characteristic absence and or an extremely low level of sulfatase activity was noticed in all the placenta obtained. In regard to the mode of delivery, pregnan … More cy was terminated by cesarean section in 47% of the cases. Spontaneous labor was observed only 27%. Sixty infants developed ichythyosis and all affected fetuses were males. The steroid sulfatase activity in female leukocytes was significantly stronger than that in normal males. Sulfatase in leukocytes obtained from the PSD babies and recessive X-linked ichthyosis patients had lower sensitivity. In the case of the mother affected with PSD, the activity was less than the half of that in normal men and the levels did not overlap with that in normal women suggesting that the measurement of leukocyte sulfatase activity would be a clinically useful tool for the diagnosis of PS @-arriers and pedigree analysis.Steroid sulfatase was purified approximately 170-fold from normal human placental microsome and properties of the enzyme were, Nnvestigated. The purified sulfatase showed a molecular weight of 500 -, OKDA on HPLC gel filtration, whereas the enzyme migrated as a molecular mass of 73KDa on sodium dodecyl sulfate polyacrylamide gel electro phoresis. Amino acid analysis revealed that the purified human placental sulfatase did not contain cystein residue. Addition of phosphatidylcholine did not enhance the enzyme activity in the placental microsomes obtained from the patients with PSD after solvilization and chromatofocusing. This result indicates that PSD is the result of defect of the enzyme rather than the defect in membrane-enzyme structure. Less

胎盘硫酸酯酶缺乏症（PSD）是一种罕见的疾病，由于胎盘酶缺乏导致雌激素分泌减少- PSD是通过体外胎盘酶测定诊断的。在日本，自1979年以来，我们已经确认了65例这种疾病。本文分析了65例鱼鳞病患儿的分娩方式、家系、新生儿出生体重、胎盘重量、生后1-3个月鱼鳞病的发生情况。此外，从正常女性和男性的外周血白细胞中分离的硫酸盐酶活性，并将该活性与PSD母亲和婴儿的活性进行比较。所获得的胎盘的硫酸酯酶的缺乏通过与β-C-DHA-硫酸酯体外孵育来证实<14>，并且活性表示为游离类固醇的量。在所有获得的胎盘中观察到特征性的缺乏和/或极低水平的硫酸酯酶活性。关于交付方式， ...更多信息 47%的病例通过剖宫产终止妊娠。自发性分娩仅占27%。60名婴儿出现心律失常，所有受影响的胎儿均为男性。女性白细胞类固醇硫酸酯酶活性明显高于正常男性。PSD患儿和隐性遗传性鱼鳞病患者外周血白细胞中硫酸酯酶的敏感性较低。在患有PSD的母亲的情况下，白细胞硫酸酯酶的活性低于正常人的一半，且与正常妇女的水平不重叠，这表明白细胞硫酸酯酶活性的测定将是临床上有用的诊断PS携带者和系谱分析的工具。类固醇硫酸酯酶从正常人胎盘微粒体纯化约170倍，调查过了纯化的硫酸酯酶在HPLC凝胶过滤上显示分子量为500 -，OKDA，而在十二烷基硫酸钠聚丙烯酰胺凝胶电泳上显示分子量为73 KDa。氨基酸分析表明，纯化的人胎盘硫酸酯酶不含半胱氨酸残基。添加磷脂酰胆碱并没有提高酶活性的胎盘微粒体从PSD患者后，溶剂化和色谱聚焦。这一结果表明PSD是酶缺陷的结果，而不是膜酶结构缺陷的结果。少

项目成果

鈴木 隆,平戸 久美子,范姜 正仁,斉藤 裕,矢内原 巧,真井 康博,真井 徳幸: "胎盤性Sulfatase欠損症の双胎例" 日産婦関東連合地方部会報. 53. 5-8 (1991)

Takashi Suzuki、Kumiko Hirato、Masahito Fan Jiang、Yutaka Saito、Takumi Yanaihara、Yasuhiro Mai、Noriyuki Mai：“胎盘硫酸酯酶缺乏症双胞胎的病例”日本妇女关东联盟地区公报 53. 5-8 (1991))。

Takashi Suzuki,Kumiko Hirato,Takumi Yanaihara,Tsuyoki kadofuku,Tsuneo Sato,Minoru Hoshino,Noboru Yanaihara: "Purification and properties of steroid sulfatase from human placenta" Endocrinologia Japonica. (1992)

Takashi Suzuki、Kumiko Hirato、Takumi Yanaihara、Tsuyoki kadofuku、Tsuneo Sato、Minoru Hoshino、Noboru Yanaihara：“人胎盘中类固醇硫酸酯酶的纯化和特性”Endocrinologia Japonica。

KUMIKO HIRATO,TAKASHI SUZUKI,TAKAAKI HONDO,HIROSHI SAITO,TAKUMI YANAIHARA: "Steroid Sulfatase Activities in Human Leukocytes:Biochemical and Clinical Aspects" Endocrinol.Japon.38. 597-602 (1991)

KUMIKO HIRATO、TAKASHI SUZUKI、TAKAAKI HONDO、HIROSHI SAITO、TAKUMI YANAIHARA：“人类白细胞中的类固醇硫酸酯酶活性：生化和临床方面”Endocrinol.Japon.38。

Kumiko Hirato, et al.: "Steroid sulfatase activities in human leukocytes : Biochemical and clinical aspects" Endocrinol Jpn. 38 : 6. 597-602 (1991)

Kumiko Hirato 等人：“人类白细胞中的类固醇硫酸酯酶活性：生化和临床方面”Endocrinol Jpn。

KUMIKO HIRATO AND TAKUMI YANAIHARA: "Serum Steroid Hormone Levels in Neonates Born from the Mother with Placental Sulfatase Deficiency" Endocrinol.Japon.37. 731-739 (1990)

KUMIKO HIRATO 和 TAKUMI YANAIHARA：“胎盘硫酸酯酶缺乏症母亲所生新生儿的血清类固醇激素水平”Endocrinol.Japon.37。