Research Institute Growth & Development (GROW), Academic Hospital Maastricht, Maastricht, The Netherlands.
Mol Hum Reprod. 2004 Jan;10(1):71-5. doi: 10.1093/molehr/gah008.
Spinocerebellar ataxia 3 (SCA3) is an autosomal dominant neurodegenerative disorder characterized by variable expression and a variable age of onset. SCA3/MJD (Machado-Joseph disease) is caused by an expansion of a (CAG)(n) repeat in the MJD1 gene on chromosome 14q32.1. A single cell PCR protocol has been developed for preimplantation genetic diagnosis (PGD) of SCA3 to select unaffected embryos on the basis of the CAG genotype. Single leukocytes and blastomeres served as a single cell amplification test system to determine the percentage of allelic drop-out (ADO) and PCR efficiency. Out of 105 tested heterozygous single leukocytes, 103 (98.1%) showed a positive amplification signal, while five cells (4.9%) showed ADO. Amplification in single blastomeres was obtained in 13 out of a total of 14, and ADO was observed in two out of the 13 single blastomeres. PGD of SCA3 was performed in a couple with paternal transmission of the SCA3 allele. Seven embryos were available for biopsy, all biopsied blastomeres showed amplification and no ADO occurred. One embryo was diagnosed as affected whereas six embryos were diagnosed as unaffected. Two unaffected embryos were transferred and resulted in a singleton pregnancy and the birth of a healthy girl.
脊髓小脑共济失调 3 型（SCA3）是一种常染色体显性遗传性神经退行性疾病，其特征是表达可变，发病年龄可变。SCA3/MJD（Machado-Joseph 病）是由 MJD1 基因中（CAG）（n）重复扩增引起的，位于 14q32.1 号染色体上。已经开发出一种单细胞 PCR 方案，用于 SCA3 的植入前基因诊断（PGD），根据 CAG 基因型选择未受影响的胚胎。单个白细胞和卵裂球作为单细胞扩增测试系统，用于确定等位基因丢失（ADO）和 PCR 效率的百分比。在 105 个测试的杂合性单个白细胞中，有 103 个（98.1%）显示出阳性扩增信号，而 5 个细胞（4.9%）显示 ADO。总共 14 个卵裂球中有 13 个获得了扩增，而在这 13 个卵裂球中有 2 个观察到 ADO。对携带 SCA3 等位基因的父系遗传的一对夫妇进行了 SCA3 的 PGD。有 7 个胚胎可用于活检，所有活检的卵裂球均显示扩增，未发生 ADO。一个胚胎被诊断为受影响，而六个胚胎被诊断为未受影响。两个未受影响的胚胎被移植，导致单胎妊娠和健康女孩的出生。
