PMID- 32500460
OWN - NLM
STAT- MEDLINE
DCOM- 20210506
LR  - 20210802
IS  - 1573-7330 (Electronic)
IS  - 1058-0468 (Print)
IS  - 1058-0468 (Linking)
VI  - 37
IP  - 8
DP  - 2020 Aug
TI  - Complex preimplantation genetic tests for Robertsonian translocation, HLA, and 
      X-linked hyper IgM syndrome caused by a novel mutation of CD40LG gene.
PG  - 2025-2031
LID - 10.1007/s10815-020-01846-y [doi]
AB  - PURPOSE: To perform complex preimplantation genetic tests (PGT) for aneuploidy 
      screening, Robertsonian translocation, HLA-matching, 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.
FAU - Huang, Sexin
AU  - Huang S
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China.
FAU - Niu, Yuping
AU  - Niu Y
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China.
FAU - Li, Jie
AU  - Li J
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China.
FAU - Gao, Ming
AU  - Gao M
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Shandong Provincial Hospital, Jinan, 250001, Shandong, China.
FAU - Yan, Junhao
AU  - Yan J
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China.
FAU - Ma, Shuiying
AU  - Ma S
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China.
FAU - Gao, Xuan
AU  - Gao X
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China.
FAU - Gao, Yuan
AU  - Gao Y
AUID- ORCID: 0000-0002-7644-2994
AD  - Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong 
      University, Jinan, 250012, Shandong, China. gaoyuan@sduivf.com.
AD  - Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong 
      University, Jinan, 250012, Shandong, China. gaoyuan@sduivf.com.
AD  - Shandong Key Laboratory of Reproductive Medicine, Jinan, 250012, Shandong, China. 
      gaoyuan@sduivf.com.
AD  - Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, 
      250012, Shandong, China. gaoyuan@sduivf.com.
AD  - National Research Center for Assisted Reproductive Technology and Reproductive 
      Genetics, Shandong University, Jinan, 250012, Shandong, China. 
      gaoyuan@sduivf.com.
LA  - eng
GR  - 2018YFC1003100/National Key Research and Development Program of China/
GR  - 2018YFC1004900/National Key Research and Development Program of China/
GR  - ZR2018PH006/Natural Science Foundation of Shandong Province/
GR  - ZR2018MC014/Natural Science Foundation of Shandong Province/
GR  - 2017G006035/Key Research and Development Program of Shandong Province/
PT  - Journal Article
DEP - 20200605
PL  - Netherlands
TA  - J Assist Reprod Genet
JT  - Journal of assisted reproduction and genetics
JID - 9206495
RN  - 0 (HLA Antigens)
RN  - 147205-72-9 (CD40 Ligand)
SB  - IM
MH  - Aneuploidy
MH  - Biopsy
MH  - Blastocyst/metabolism
MH  - CD40 Ligand/*genetics
MH  - Female
MH  - Fertilization in Vitro
MH  - Genetic Testing/trends
MH  - HLA Antigens/*genetics
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Hyper-IgM Immunodeficiency Syndrome, Type 1/*diagnosis/genetics/pathology
MH  - Pregnancy
MH  - *Preimplantation Diagnosis
MH  - Sperm Injections, Intracytoplasmic
MH  - Translocation, Genetic/genetics
PMC - PMC7468018
OTO - NOTNLM
OT  - CD40LG
OT  - HLA
OT  - PGT
OT  - Robertsonian translocation
OT  - XHIGM
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2020/06/06 06:00
MHDA- 2021/05/07 06:00
PMCR- 2021/08/01
CRDT- 2020/06/06 06:00
PHST- 2020/04/08 00:00 [received]
PHST- 2020/05/28 00:00 [accepted]
PHST- 2020/06/06 06:00 [pubmed]
PHST- 2021/05/07 06:00 [medline]
PHST- 2020/06/06 06:00 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - 10.1007/s10815-020-01846-y [pii]
AID - 1846 [pii]
AID - 10.1007/s10815-020-01846-y [doi]
PST - ppublish
SO  - J Assist Reprod Genet. 2020 Aug;37(8):2025-2031. doi: 10.1007/s10815-020-01846-y. 
      Epub 2020 Jun 5.