Increased levels of plasma lysosomal enzymes in patients with Lowe syndrome.
Increased levels of plasma lysosomal enzymes in patients with Lowe syndrome.
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Lowe综合征患者血浆溶酶体酶水平升高。
DOI：
10.1073/pnas.96.23.13342
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发表时间：
1999
影响因子：
11.1
通讯作者：
Majerus,PW
中科院分区：
文献类型：
--
作者：
Ungewickell,AJ;Majerus,PW
洛威综合征是一种X连锁疾病，具有复杂的表型，包括进行性肾功能衰竭和失明。这种疾病是由一种名为OCRL的肌醇多聚5-磷酸酶突变引起的。结果表明，OCRL蛋白存在于溶酶体表面，OCRL缺失的肾小管上皮细胞系积累底物磷脂酰肌醇4，5-二磷酸。由于这种脂质是溶酶体转运囊泡所必需的，我们推测Lowe综合征患者的溶酶体酶转运存在缺陷，导致细胞外溶酶体酶的增加，并可能导致组织损伤并参与疾病的发病。我们检测了15例Lowe综合征患者和15例年龄匹配的男性对照组血浆中的7种溶酶体酶。我们发现所有测量的酶都增加了1.6到2.0倍。当按所有酶的活性的五分之一分析数据时，我们发现最低五分之一的值95%来自正常受试者，而最高的五分之一的值85%来自洛威综合征患者。酶水平的升高不是由于肾功能不全，因为肌酐水平最高的4名患者的酶活性与肌酐水平最低的6名患者的酶活性没有差异。
Lowe syndrome is an X-linked disorder that has a complex phenotype that includes progressive renal failure and blindness. The disease is caused by mutations in an inositol polyphosphate 5-phosphatase designated OCRL. It has been shown that the OCRL protein is found on the surface of lysosomes and that a renal tubular cell line deficient in OCRL accumulated substrate phosphatidylinositol 4,5-bisphosphate. Because this lipid is required for vesicle trafficking from lysosomes, we postulate that there is a defect in lysosomal enzyme trafficking in patients with Lowe syndrome that leads to increased extracellular lysosomal enzymes and might lead to tissue damage and contribute to the pathogenesis of the disease. We have measured seven lysosomal enzymes in the plasma of 15 patients with Lowe syndrome and 15 age-matched male controls. We find a 1.6- to 2.0-fold increase in all of the enzymes measured. When the data was analyzed by quintiles of activity for all of the enzymes, we found that 95% of values in the lowest quintile come from normal subjects whereas in the highest quintile 85% of the values are from patients with Lowe syndrome. The increased enzyme levels are not attributable to renal insufficiency because there was no difference in enzyme activity in the four patients with the highest creatinine levels compared with the six patients with the lowest creatinine values.
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影响因子：
5
作者：
HULTBERG, B;ISAKSSON, A;OCKERMAN, PA
通讯作者：
OCKERMAN, PA
DOI：
10.1002/ajmg.1320590304
发表时间：
1995-11-20
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
KENWORTHY, L;CHARNAS, L
通讯作者：
CHARNAS, L
DOI：
10.1073/pnas.92.11.4853
发表时间：
1995-05-23
影响因子：
11.1
作者：
ZHANG, XL;JEFFERSON, AB;MAJERUS, PW
通讯作者：
MAJERUS, PW
Lowe 综合征家族生殖系嵌合体的表征，以及 OCRL1 基因中七个新突变的鉴定。
影响因子：
9.8
作者：
V. Satre;Nicole Monnier;Florence Berthoin;C. Ayuso;Alain Joannard;P. Jouk;Isidora López;André Megabarne;Henri Jean Philippe;Henri Plauchu;María Luisa de Torres;Joël Lunardi
通讯作者：
Joël Lunardi
日本 Lowe 综合征家族中 OCRLI 基因的两个新突变的鉴定
影响因子：
3.5
作者：
T. Kubota;A. Sakurai;Kazuo Arakawa;Mitsunobu Shirnazu;K. Wakui;K. Furihata;Yoshimitsu Fukushirna
通讯作者：
Yoshimitsu Fukushirna