1个X-连锁鱼鳞病家系的基因突变鉴定与产前诊断

Identification of gene mutation and prenatal diagnosis in a family with X-linked ichthyosis

摘要:

X-连锁鱼鳞病 （XLI）是一种类固醇硫酸酯酶缺乏的代谢性疾病，常于出生时或生后不久发病，编码类固醇硫酸酯酶的基因 （STS）位于X染色体短臂上，STS基因发生缺失或突变时可导致此病的发生。本研究收集一个家系的临床表型资料，其中先证者，男，足月顺产，11岁，全身皮肤干燥、粗糙、呈黑褐色鳞片状，主要累及腹部和肢体伸侧。采集家系中各成员的外周血提取DNA，采用多重连接依赖式探针扩增 （MLPA）技术对家系各成员的X染色体上的STS基因拷贝数进行检测，用全基因组芯片进一步明确X染色体微缺失片段的大小，随后采用MLPA技术对先证者母亲再生育进行产前诊断。结果发现家系中先证者及2个患者均为STS缺失的男性半合子，基因芯片鉴定出Xp22.31存在缺失，缺失大小为1.6Mb （chrX：6，516，735-8，131，442），另鉴定出2个女性家庭成员为携带者。先证者母亲再生育产前诊断结果证实胎儿为携带者。本研究表明该XLI家系存在STS基因缺失，该缺失引发出XLI特有的皮肤病变，MLPA是XLI分子诊断与产前诊断的便捷可靠技术。

Abstract:

X-linked ichthyosis (XLI) is a metabolic disease with steroid sulfatase deficiency and often occurs at birth or shortly after birth. The encoding gene of steroid sulfatase, STS, is located on the short arm of the X chromosome, and STS deletion or mutation can lead to the development of this disease. This study collected the data on the clinical phenotype from a family, and the proband, a boy aged 11 years with full-term vaginal delivery, had dry and rough skin and black-brown scaly patches, mainly in the abdomen and extensor aspect of extremities. Peripheral blood samples were collected from each family member and DNA was extracted. Multiplex ligation-dependent probe amplification (MLPA) was used to measure the copy number of STS on the X chromosome. Whole-genome microarray was used to determine the size of the segment with microdeletion in the X chromosome. MLPA was then used for prenatal diagnosis for the mother of the proband. The results revealed that the proband and another two male patients had hemizygotes in STS deletion. Gene microarray identified a rare deletion with a size of 1.6 Mb at Xp22.31 (chrX:6,516,735-8,131,442). Two female family members were found to be carriers. Prenatal diagnosis showed that the fetus carried by the proband's mother was a carrier of this microdeletion. This study showed STS gene deletion in this family of XLI, which causes the unique skin lesions of XLI. MLPA is a convenient and reliable technique for the molecular and prenatal diagnosis of XLI.