Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3β-hydroxysteroid-Δ5-desaturase
Lathosterolosis, a novel multiple-malformation/mental retardation syndrome due to deficiency of 3β-hydroxysteroid-Δ5-desaturase
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DOI：
10.1086/342668
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发表时间：
2002-10-01
影响因子：
9.8
通讯作者：
Parenti, G
中科院分区：
文献类型：
--
作者：
Brunetti-Pierri, N;Corso, G;Parenti, G
我们报告的临床，生化和分子特征的患者与一个新的缺陷，胆固醇生物合成。该患者表现为复杂的表型，包括多种先天性异常、智力低下和肝脏疾病。在病人的血浆和细胞中，我们发现了增加的脂甾醇水平。患者的成纤维细胞中胆固醇的生物合成是有缺陷的，显示出在将胆甾醇转化为7-脱氢胆固醇中的阻断。参与该反应的3 β-羟基类固醇-δ（5）-去饱和酶（SC 5D）的活性在患者的成纤维细胞中缺乏。患者DNA中SC 5D基因的序列分析显示存在两个错义突变（R29 Q和G211 D），证实患者受到胆固醇生物合成新缺陷的影响。
We report the clinical, biochemical, and molecular characterization of a patient with a novel defect of cholesterol biosynthesis. This patient presented with a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. In the patient's plasma and cells, we found increased levels of lathosterol. The biosynthesis of cholesterol in the patient's fibroblasts was defective, showing a block in the conversion of lathosterol into 7-dehydrocholesterol. The activity of 3beta-hydroxysteroid-Delta(5)-desaturase (SC5D), the enzyme involved in this reaction, was deficient in the patient's fibroblasts. Sequence analysis of the SC5D gene in the patient's DNA, showing the presence of two missense mutations (R29Q and G211D), confirmed that the patient is affected by a novel defect of cholesterol biosynthesis.