PRENATAL DETECTION OF THE CHOLESTEROL BIOSYNTHETIC DEFECT IN THE SMITH-LEMLI-OPITZ SYNDROME BY THE ANALYSIS OF AMNIOTIC LIQUID STEROLS
PRENATAL DETECTION OF THE CHOLESTEROL BIOSYNTHETIC DEFECT IN THE SMITH-LEMLI-OPITZ SYNDROME BY THE ANALYSIS OF AMNIOTIC LIQUID STEROLS
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DOI：
10.1002/ajmg.1320560309
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发表时间：
1995-04-10
期刊：
影响因子：
--
通讯作者：
SALEN, G
中科院分区：
文献类型：
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作者：
ABUELO, DN;TINT, GS;SALEN, G
Smith-Lemli-Opitz（SLO 或 RSH）综合征是一种常染色体隐性遗传疾病，其特征是可识别的轻微面部异常、许多器官先天性异常、发育迟缓和智力低下。其原因是胆固醇生物合成的缺陷，其特征是血浆胆固醇水平异常低，并且胆固醇前体 7 脱氢胆固醇 (7DHC) 的浓度比正常值高出数千倍。我们使用毛细管柱气相色谱法对曾生过受影响儿子的杂合母亲的羊水、羊膜细胞、血浆、胎盘和母乳中的甾醇以及她受影响的新生女儿的脐带血和血浆中的甾醇进行定量。妊娠 16 周时羊水中的胆固醇浓度正常，但通常检测不到的 7DHC 却大幅升高。在培养的羊水细胞中，7DHC 的水平为总胆固醇的 11%，与 SLO 综合征患者培养的成纤维细胞相似。 38周时，一名表型与该综合征相符的女孩出生了。 12 周时，脐带血和婴儿血浆中的胆固醇浓度异常低，而 7DHC 水平明显升高，证实了产前诊断。母亲的血浆胆固醇在妊娠期间稳步增加，但仍低于正常对照女性报告的 95% 下限。我们的结论是，现在可以通过分析羊水甾醇来检测妊娠 16 周时的 SLO 综合征，(C) 1995 Wiley-Liss, Inc.
The Smith-Lemli-Opitz (SLO or RSH) syndrome is an autosomal recessive disorder characterized by a recognizable pattern of minor facial anomalies, congenital anomalies of many organs, failure to thrive, and mental retardation. Its cause is a defect in cholesterol biosynthesis characterized by abnormally low plasma cholesterol levels and concentrations of the cholesterol precursor 7 dehydrocholesterol (7DHC) elevated up to several thousand-fold above normal. We used capillary column gas-chromatography to quantify sterols in amniotic fluid, amniotic cells, plasma, placenta, and breast milk from a heterozygous mother who had previously given birth to an affected son and in cord blood and plasma from her affected newborn daughter. The cholesterol concentration in amniotic fluid at 16 weeks gestation was normal, but 7DHC, normally undetectable, was greatly elevated. In cultured amniocytes, the level of 7DHC was 11% of total cholesterol, similar to cultured fibroblasts from patients with SLO syndrome. At 38 weeks, a girl with phenotype consistent with the syndrome was born. Cholesterol concentrations were abnormally low in cord blood and in the baby's plasma at 12 weeks, while levels of 7DHC were grossly elevated, confirming the prenatal diagnosis. The mother's plasma cholesterol increased steadily during gestation but remained below the lower 95% limit reported for normal control women. We conclude that it is now possible to detect the SLO syndrome at 16 weeks gestation by analyzing amniotic fluid sterols, (C) 1995 Wiley-Liss, Inc.