脆性X综合征的基因诊断与产前诊断

为了探讨简便、快速、准确、价廉的脆性X综合征的诊断方法，对6个智能低下家系进行了细胞遗传学检查，以及PCR直接扩增FMR1 5^'端(CGG)_{n重复序列、RT-PCR扩增FMR1基因的cDNA序列的分子遗传学检查。A家系先证者脆性X染色体高表达（35/273），分子遗传学检查证实为脆性X综合征全突变患者；B家系先证者及其母亲无脆性X染色体表达，分子遗传学检查证实为非脆性X综合征患者；C家系的男性胎儿脆性X染色体表达（5/93）,先证者及其母亲未发现脆性X染色体，分子遗传学检查证实男性胎儿为脆性X综合征全突变患者，其母亲为前突变携带者，哥哥为嵌合体患者；D家系先证者脆性X染色体高表达17%，其姐姐脆性X染色体5%，分子遗传学检查证实先证者为脆性X综合征全突变患者，其姐姐为嵌合体患者；E家系先证者及其母亲，F家系先证者发现可疑脆性X染色体，分子遗传学检查证实为非脆性X综合征家系。结论： PCR直接扩增FMR1基因(CGG)n重复序列联合RT-PCR扩增FMR1基因cDNA 序列简便、快速、价廉。可用于脆性X综合征的筛查、诊断及产前诊断，有推广应用价值。}

Genetic Diagnosis and Prenatal Genetic Diagnosis of Fragile X Syndrome

In order to obtain a simple,fast,accurate and low-cost diagnosis method of fragile X syndrome, cytogenetic tests and molecular genetic tests were carried out with direct amplification of (CGG)(n) repeat sequence in 5' terminal of FMR1 gene by PCR and the cDNA sequence of FMR1 by RT-PCR from six mental retardation pedigrees. The proband of pedigree A with high expression of fragile X chromosome(35/273) was detected to be a full mutation patient of fragile X syndrome by the molecular genetic test. There is no expression of fragile X chromosome in the proband and his mother of pedigree B, which was further confirmed as a non-fragile X pedigree by the molecular genetic test. A male foetus of the pedigree C has fragile X chromosome(5/93), but the proband and his mother has no fragile X chromosome. By further detection using molecular genetic test, the male foetus is a full mutation patient of fragile X syndrome, his mother is a permutated carrier, and his brother is a mosaic patient. The proband of pedigree D has high expression of fragile X chromosome (17%), his sister also has expression of fragile X chromosome (5%). By further detection with molecular genetic test, the proband is a full mutation patient of fragile X syndrome,and his sister is a mosaic patient. The probands of pedigrees E and F of the mother were found with suspicions fragile X chromosome, being confirmed as the non-fragile X pedigrees by the molecular genetic test. The conclusion is that the analysis test with direct amplification of 5'j(CGG)n repeat sequence and cDNA sequence in FMR1 gene is simple,fast,low-cost and can be applied in screening, diagnosis and prenatal diagnosis of fragile X syndrome.