Expanded carrier screening and preimplantation genetic diagnosis in a couple who delivered a baby affected with congenital factor VII deficiency.
Expanded carrier screening and preimplantation genetic diagnosis in a couple who delivered a baby affected with congenital factor VII deficiency.
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对一对产下患有先天性因子 VII 缺乏症的婴儿的夫妇进行了扩大的携带者筛查和植入前遗传学诊断。
DOI：
10.1186/s12881-018-0525-9
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发表时间：
2018-01-24
影响因子：
--
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
He WB;Tan YQ;Hu X;Li W;Xiong B;Luo KL;Gong F;Lu GX;Lin G;Du J
胚胎植入前遗传学诊断（PGD）是防止孟德尔遗传病代代相传的有力工具。然而，PGD只能识别单基因遗传疾病，而不能识别其他潜在的单基因疾病。我们的目的是使用PGD提供一个健康的婴儿没有先天性FVII缺乏症或其他常见的孟德尔疾病的夫妇，其中两个人都携带有害的突变F7基因。在通过桑格测序确认这对夫妇的两名成员都是F7基因突变的携带者后，对623种隐性遗传疾病进行了扩大的携带者筛查（ECS），以检测其他基因的病理突变。采用PGD和预分化遗传学筛查（PGS）排除胚胎单基因异常和非整倍体。使用靶向捕获测序技术的ECS显示，这对夫妇在CFTR基因中携带杂合致病突变c.3659C > T（p.Thr1220Ile）和c.3209G > A（p.Arg1070Gln）。在PGD和PGS之后，移植了他们的一个没有先天性FVII缺陷、囊性纤维化（CF）和非整倍体的胚胎，导致了一个健康的3200 g男婴的出生。据我们所知，我们首次成功地对先天性FVII缺乏症和ECS后的PGD进行了PGD，以排除CF。我们的工作显着改善了夫妇的生殖结果，并提供了一个明确的例子，使用ECS结合PGD，以避免交付的后代不仅受到确定的单基因遗传性疾病，但也受到其他潜在的单基因病理和非整倍性。
Preimplantation genetic diagnosis (PGD) is a powerful tool for preventing the transmission of Mendelian disorders from generation to generation. However, PGD only can identify monogenically inherited diseases, but not other potential monogenic pathologies. We aimed to use PGD to deliver a healthy baby without congenital FVII deficiency or other common Mendelian diseases in a couple in which both individuals carried a deleterious mutation in the F7 gene. After both members of the couple were confirmed to be carriers of the F7 gene mutation by Sanger sequencing, expanded carrier screening (ECS) for 623 recessive inheritance diseases was performed to detect pathological mutations in other genes. PGD and preimplantational genetic screening (PGS) were employed to exclude monogenic disorders and aneuploidy for their embryos. ECS using targeted capture sequencing technology revealed that the couple carried the heterozygous disease-causative mutations c.3659C > T (p.Thr1220Ile) and c.3209G > A (p.Arg1070Gln) in the CFTR gene. After PGD and PGS, one of their embryos that was free of congenital FVII deficiency, cystic fibrosis (CF) and aneuploidy was transferred, resulting in the birth of a healthy 3200 g male infant. We successfully implemented PGD for congenital FVII deficiency and PGD after ECS to exclude CF for the first time to the best of our knowledge. Our work significantly improved the reproductive outcome for the couple and provides a clear example of the use of ECS combined with PGD to avoid the delivery of offspring affected not only by identified monogenically inherited diseases but also by other potential monogenic pathologies and aneuploidy.
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影响因子：
158.5
作者：
Girelli, D;Russo, C;Corrocher, R
通讯作者：
Corrocher, R
影响因子：
6.7
作者：
Mariani, G;Herrmann, FH;Bernardi, F
通讯作者：
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6.7
作者：
Eldar-Geva, Talia;Srebnik, Naama;Schimmel, Michael S.
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Schimmel, Michael S.
影响因子：
4
作者：
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通讯作者：
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影响因子：
6.7
作者：
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通讯作者：
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