Oyama N, Satoh M, Iwatsuki K, Kaneko F
Department of Dermatology, Fukushima Medical University School of Medicine, Japan.
J Invest Dermatol. 2000 Jun;114(6):1195-9. doi: 10.1046/j.1523-1747.2000.00004.x.
X-linked ichthyosis is caused by steroid sulfatase deficiency which results from abnormalities in its coding gene. The majority of X-linked ichthyosis patients ( approximately 90%) have complete or partial deletions of the steroid sulfatase gene. In this study, we examined the mutations of the steroid sulfatase gene in two unrelated X-linked ichthyosis patients without complete deletion of the gene. Polymerase chain reaction-single-strand conformation polymorphism and direct sequencing analyses showed that each patient has a different single base pair substitution within exon 8 encoding the C-terminal half of the steroid sulfatase polypeptide. Both mutations resulted in the transversion of functional amino acids: a G-->C substitution at nucleotide 1344, causing a predicted change of a glycine to an arginine, and a C-->T substitution at nucleotide 1371, causing a change from a glutamine to a stop codon. In vitro steroid sulfatase cDNA expression using site-directed mutagenesis revealed that these mutations are in fact pathogenic and reflect the levels of steroid sulfatase enzyme activities in each of the X-linked ichthyosis patients.
X连锁鱼鳞病由类固醇硫酸酯酶缺乏引起，该酶缺乏是由其编码基因异常所致。大多数X连锁鱼鳞病患者（约90%）存在类固醇硫酸酯酶基因的完全或部分缺失。在本研究中，我们检测了两名无该基因完全缺失的非亲缘关系X连锁鱼鳞病患者的类固醇硫酸酯酶基因突变情况。聚合酶链反应-单链构象多态性分析和直接测序分析表明，每名患者在编码类固醇硫酸酯酶多肽C端一半的第8外显子内都有一个不同的单碱基对替换。这两种突变均导致功能性氨基酸的颠换：第1344位核苷酸由G替换为C，导致预测的甘氨酸变为精氨酸；第1371位核苷酸由C替换为T，导致谷氨酰胺变为终止密码子。使用定点诱变进行的体外类固醇硫酸酯酶cDNA表达显示，这些突变实际上具有致病性，并反映了每名X连锁鱼鳞病患者体内类固醇硫酸酯酶的活性水平。
