PDF(Pubmed)
Abstract：
7-dehydrocholesterol (7-DHC) and cholesterol (CHOL) are biomarkers of Smith-Lemli-Opitz Syndrome (SLOS), a congenital autosomal recessive disorder characterized by elevated 7-DHC level in patients. Hair samples have been shown to have great diagnostic and research value, which has long been neglected in the SLOS field. In this study, we sought to investigate the feasibility of using hair for SLOS diagnosis. In the presence of antioxidants (2,6-ditert-butyl-4-methylphenol and triphenylphosphine), hair samples were completely pulverized and extracted by micro-pulverized extraction in alkaline solution or in n-hexane. After microwave-assisted derivatization with N,O-Bis(trimethylsilyl)trifluoroacetamide, the analytes were measured by GC-MS. We found that the limits of determination for 7-DHC and CHOL were 10 ng/mg and 8 ng/mg, respectively. In addition, good linearity was obtained in the range of 50-4000 ng/mg and 30-6000 ng/mg for 7-DHC and CHOL, respectively, which fully meets the requirement for SLOS diagnosis and related research. Finally, by applying the proposed method to real hair samples collected from 14 healthy infants and two suspected SLOS patients, we confirmed the feasibility of hair analysis as a diagnostic tool for SLOS. In conclusion, we present an optimized and validated analytical method for the simultaneous determination of two SLOS biomarkers using human hair.
摘要：
7-脱氢胆固醇（7-DHC）和胆固醇（CHOL）是Smith-Lemli-Opitz综合征（SLOS）的生物标志物，一种先天性常染色体隐性遗传疾病，其特征是患者的7-DHC水平升高。头发样本已被证明具有巨大的诊断和研究价值，这在SLOS领域一直被忽视。在这项研究中,我们试图研究使用毛发进行SLOS诊断的可行性.在抗氧化剂（2,6-二叔丁基-4-甲基苯酚和三苯基膦）的存在下，头发样品被完全粉碎，并在碱性溶液或正己烷中通过微粉碎提取进行提取。在用N进行微波辅助衍生后，O-双(三甲基甲硅烷基)三氟乙酰胺,通过GC-MS测量分析物。我们发现7-DHC和CHOL的测定极限分别为10ng/mg和8ng/mg，分别。此外,对于7-DHC和CHOL，在50-4000ng/mg和30-6000ng/mg的范围内获得了良好的线性，分别,完全满足SLOS诊断和相关研究的要求。最后,通过将提出的方法应用于从14名健康婴儿和两名疑似SLOS患者收集的真实头发样本，我们证实了头发分析作为SLOS诊断工具的可行性.总之,我们提出了一种优化和验证的分析方法,用于使用人发同时测定两种SLOS生物标志物.
