Qubbaj Wafa, Al-Aqeel Aida I, Al-Hassnan Zuhair, Al-Duraihim Adel, Awartani Khalid, Al-Rejjal Rafat, Coskun Serdar
Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Prenat Diagn. 2008 Oct;28(10):900-3. doi: 10.1002/pd.2081.
Morquio syndrome is an autosomal recessive disease and mutations in the N-acetylgalactosamine 6-sulfate sulfatase (GALNS) gene cause Morquio type A disease. Preimplantation genetic diagnosis (PGD), an early form of prenatal diagnosis for couples at risk of transmitting inherited diseases, was applied to prevent transmission of this disease.
A couple with three affected children, having homozygous W159C (p. Trp 159 Cys) mutation in GALNS gene, underwent in vitro fertilization (IVF) treatment and PGD. Mutation analyses from the embryos were performed following whole genome amplification of single blastomeres using multiple displacement amplification (MDA).
Three embryos were diagnosed as normal and two were transferred on day 4. The cycle resulted in a pregnancy and a live birth of a carrier male infant. Genetic haplotyping analysis of the infant and the leftover MDA samples enabled us to determine which embryo was implanted. The discrepancy in results was explained by allele dropout (ADO) of the mutant allele from the MDA product.
A feasible strategy for PGD of Morquio disease including whole genome amplification by MDA and the use of preimplantation genetic haplotyping is described. MDA product archiving will be useful for future investigations if needed.
黏多糖贮积症IV型是一种常染色体隐性疾病,N-乙酰半乳糖胺6-硫酸酯酶(GALNS)基因突变导致黏多糖贮积症A型疾病。胚胎植入前遗传学诊断(PGD)作为一种为有遗传性疾病传播风险的夫妇提供的早期产前诊断方式,被用于预防该疾病的传播。
一对育有三个患病子女且GALNS基因存在纯合W159C(p.Trp 159 Cys)突变的夫妇,接受了体外受精(IVF)治疗及PGD。使用多重置换扩增(MDA)对单个卵裂球进行全基因组扩增后,对胚胎进行突变分析。
三个胚胎被诊断为正常,其中两个在第4天被移植。该周期妊娠成功并产下一名携带致病基因的男婴。对婴儿及剩余MDA样本进行的遗传单倍型分析使我们能够确定植入的是哪个胚胎。结果差异可通过MDA产物中突变等位基因的等位基因脱扣(ADO)来解释。
本文描述了一种针对黏多糖贮积症IV型PGD的可行策略,包括通过MDA进行全基因组扩增及使用胚胎植入前遗传单倍型分析。如有需要,MDA产物存档将有助于未来的研究。