Complex preimplantation genetic tests for Robertsonian translocation, HLA, and X-linked hyper IgM syndrome caused by a n
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GENETICS
Complex preimplantation genetic tests for Robertsonian translocation, HLA, and X-linked hyper IgM syndrome caused by a novel mutation of CD40LG gene Sexin Huang 1,2,3,4,5 & Yuping Niu 1,2,3,4,5 & Jie Li 1,2,3,4,5 & Ming Gao 1,2,3,4,5 & Yan Zhang 6 & Junhao Yan 1,2,3,4,5 & Shuiying Ma 1,2,3,4,5 & Xuan Gao 1,2,3,4,5 & Yuan Gao 1,2,3,4,5 Received: 8 April 2020 / Accepted: 28 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose To perform complex preimplantation genetic tests (PGT) for aneuploidy screening, Robertsonian translocation, HLAmatching, and X-linked hyper IgM syndrome (XHIGM) caused by a novel mutation c.156 G>T of CD40LG gene. Methods Reverse transcription PCR (RT-PCR) and Sanger sequencing were carried out to confirm the causative variant of CD40LG gene in the proband and parents. Day 5 and D6 blastocysts, obtained by in vitro fertilization (IVF) with intracytoplasmic sperm injection, underwent trophectoderm (TE) biopsy and whole genomic amplification (WGA) and next generation sequencing (NGS)-based PGT to detect the presence of a maternal CD40LG mutation, aneuploidy, Robertsonian translocation carrier, and human leukocyte antigen (HLA) haplotype. Results Sanger sequencing data of the genomic DNA showed that the proband has a hemizygous variant of c. 156 G>T in the CD40LG gene, while his mother has a heterozygous variant at the same position. Complementary DNA (cDNA) of CD40LG amplification and sequencing displayed that no cDNA of CD40LG was found in proband, while only wild-type cDNA of CD40LG was amplified in the mother. PGT results showed that only one of the six tested embryos is free of the variant c.156 G>T and aneuploidy and having the consistent HLA type as the proband. Meanwhile, the embryo is a Robertsonian translocation carrier. The embryo was transplanted into the mother’s uterus. Amniotic fluid testing results are consistent with that of PGT. A healthy baby girl was delivered, and the peripheral blood testing data was also consistent with the testing results of transplanted embryo. Conclusions The novel mutation of c. 156 G>T in CD40LG gene probably leads to XHIGM by nonsense-meditated mRNA decay (NMD), and complex PGT of preimplantation genetic testing for monogenic disease (PGT-M), aneuploidy (PGT-A), structural rearrangement (PGT-SR), and HLA-matching (PGT-HLA) can be performed in pedigree with both X-linked hyper IgM syndrome and Robertsonian translocation. Keywords XHIGM . CD40LG . Robertsonian translocation . HLA . PGT * Yuan Gao [email protected] 1
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China
2
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan 250012, Shandong, China
3
Shandong Key Laboratory of Reproductive Medicine, Jinan 250012, Shandong, China
4
Shandong Provincial Clinical Research Center for Reproductive Health, Jinan 250012, Shandong, China
5
National Research Center for Assisted Reproductive Technology
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