【摘要】 目的胚胎植入前遗传学诊断技术(PGD)是减少出生缺陷儿的有效方法。遗传咨询和预实验是PGD流程关键环节,影响着PGD最终结局。方法根据遗传病的遗传方式不同,设计个性化预实验策略,包括家系突变位点验证,单细胞基因组扩增测序,连锁分析。结果遗传咨询结合预实验中突变位点在家系成员中的验证结果,可以判断常染色体显性和X-连锁隐性遗传病致病基因及基因突变位点的可靠性,而对于X-连锁隐性遗传病致病基因的寻找,需从家族中的先症者入手而非携带者。与此同时,预实验还能发现家系中存在的一些特殊问题,比如染色体平衡易位。结论遗传咨询和预实验,需成为单基因遗传病胚胎诊断流程的第一步,可以帮助我们判断基因及基因突变位点的致病性,制定个性化单基因胚胎检测策略,提高诊断的准确性,将因基因或者突变位点判断错误而导致的患儿出生风险降到最小。更多还原

【Abstract】 Objective Preimplantation genetic diagnosis (PGD) is one of effective strategies to block the transmission of genetic diseases in the family and to reduce birth defects. During the whole process of PGD,genetic counseling and preliminary experiment will be the very important steps. The strategies and methods of preliminary experiments may affect the final outcome. Methods Individualized preliminary experiment strategies were designed based on the different hereditary patterns of diseases,including gene mutations verification and single cell genomic amplification and sequencing. Results The reliability of pathogenic genes and their mutation sites for autosomal dominant and X-linked recessive hereditary diseases can be evaluated by genetic counseling combined with pre-experiments results including mutation sites identification in family members. The gene testing of a X-linked recessive hereditary disease should start with the probands in the family rather than carriers. Furthermore,some special problems in the couples,such as balanced chromosome translocation,can also be identified by pre-experiments. Conclusion Genetic counseling and pre-experiment should be the first step in the process of single gene embryo diagnosis. It can help us to evaluate the pathogenicity of genes and gene mutation sites,design personalized embryo testing strategies,improve the accuracy of diagnosis,and minimize the risk of delivering a baby with birth defects.更多还原