Prevention of recurrence of severe combined immunodeficiency through preimplantation genetic testing: a case study of a novel IL2RG variant and confirmed maternal somatic mosaicism in Thailand
- 1Gift Fertility Co., Ltd., Bangkok, Thailand
- 2Nakornthon Gift Fertility Center, Bangkok, Thailand
Abstract
Research question: Can preimplantation genetic testing for monogenic disorders (PGT-M) be effectively implemented to prevent recurrence of X-linked severe combined immunodeficiency (X-SCID) caused by a novel IL2RG variant when conventional parental carrier testing initially yields a negative result?
Design: Case report: A Thai couple with a prior affected child (deceased; T⁻B⁺NK⁻ immunophenotype; IL2RG c.676C > G, p.(Arg226Gly)) underwent whole exome sequencing (WES), which was initially negative in both parents. Subsequent WES reanalysis identified a low-level heterozygous signal (~ 12% allele frequency) in the mother's blood, below the standard 30% calling threshold, consistent with low-level maternal mosaicism. Direct sequencing and PCR–RFLP from buccal swab tissue showed a concordant low-level signal in a second tissue compartment. Six blastocysts obtained via ICSI underwent trophectoderm biopsy for combined PGT-M (targeted to the proband's confirmed variant) and comprehensive chromosomal screening (PGT-A).
Results: Four blastocysts were euploid and two aneuploids. Of the euploid embryos, three were mutation-free (wild-type) and one carried the IL2RG c.676C > G variant. A single frozen-thawed embryo transfer of a mutation-free euploid embryo resulted in a confirmed intrauterine pregnancy. Non-invasive prenatal testing (NIPT) at 12 weeks demonstrated low risk for Trisomy 21, 18, and 13, with fetal sex concordant with PGT-A findings.
Conclusions: The novel IL2RG c.676C > G (p.(Arg226Gly)) variant identified at a known mutational hotspot (codon 226) and absent from global variant databases is classified as Likely Pathogenic per ACMG criteria. Low-level maternal mosaicism was subsequently identified in blood and supported by concordant low-level findings in buccal mucosa, clarifying recurrence-risk counselling for this family. PGT-M anchored to the proband's confirmed IL2RG variant successfully identified three transferable, euploid, mutation-free embryos, and transfer of one embryo resulted in an ongoing pregnancy. This case demonstrates that ICSI with PGT-M can prevent X-SCID recurrence even when standard parental carrier testing is initially non-informative, establishing a reproductive workflow applicable to families in whom the proband's variant is confirmed.
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BibTeX
@article{koonthaweelab2026prevention,
title = {{Prevention of recurrence of severe combined immunodeficiency through preimplantation genetic testing: a case study of a novel IL2RG variant and confirmed maternal somatic mosaicism in Thailand}},
author = {Rattanamon Koonthaweelab and Napadon Yaibuates and Pongpet Benjaponwattana and Busarin Boonyacheeva and Jitti Saksantisuk},
journal = {Journal of Assisted Reproduction and Genetics},
year = {2026},
month = jul,
doi = {10.1007/s10815-026-03985-0},
url = {https://doi.org/10.1007/s10815-026-03985-0},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Prevention of recurrence of severe combined immunodeficiency through preimplantation genetic testing: a case study of a novel IL2RG variant and confirmed maternal somatic mosaicism in Thailand
AU - Rattanamon Koonthaweelab
AU - Napadon Yaibuates
AU - Pongpet Benjaponwattana
AU - Busarin Boonyacheeva
AU - Jitti Saksantisuk
PY - 2026
DA - 2026/07/28
JO - Journal of Assisted Reproduction and Genetics
DO - 10.1007/s10815-026-03985-0
UR - https://doi.org/10.1007/s10815-026-03985-0
AB - Research question: Can preimplantation genetic testing for monogenic disorders (PGT-M) be effectively implemented to prevent recurrence of X-linked severe combined immunodeficiency (X-SCID) caused by a novel IL2RG variant when conventional parental carrier testing initially yields a negative result? Design: Case report: A Thai couple with a prior affected child (deceased; T⁻B⁺NK⁻ immunophenotype; IL2RG c.676C > G, p.(Arg226Gly)) underwent whole exome sequencing (WES), which was initially negative in both parents. Subsequent WES reanalysis identified a low-level heterozygous signal (~ 12% allele frequency) in the mother's blood, below the standard 30% calling threshold, consistent with low-level maternal mosaicism. Direct sequencing and PCR–RFLP from buccal swab tissue showed a concordant low-level signal in a second tissue compartment. Six blastocysts obtained via ICSI underwent trophectoderm biopsy for combined PGT-M (targeted to the proband's confirmed variant) and comprehensive chromosomal screening (PGT-A). Results: Four blastocysts were euploid and two aneuploids. Of the euploid embryos, three were mutation-free (wild-type) and one carried the IL2RG c.676C > G variant. A single frozen-thawed embryo transfer of a mutation-free euploid embryo resulted in a confirmed intrauterine pregnancy. Non-invasive prenatal testing (NIPT) at 12 weeks demonstrated low risk for Trisomy 21, 18, and 13, with fetal sex concordant with PGT-A findings. Conclusions: The novel IL2RG c.676C > G (p.(Arg226Gly)) variant identified at a known mutational hotspot (codon 226) and absent from global variant databases is classified as Likely Pathogenic per ACMG criteria. Low-level maternal mosaicism was subsequently identified in blood and supported by concordant low-level findings in buccal mucosa, clarifying recurrence-risk counselling for this family. PGT-M anchored to the proband's confirmed IL2RG variant successfully identified three transferable, euploid, mutation-free embryos, and transfer of one embryo resulted in an ongoing pregnancy. This case demonstrates that ICSI with PGT-M can prevent X-SCID recurrence even when standard parental carrier testing is initially non-informative, establishing a reproductive workflow applicable to families in whom the proband's variant is confirmed.
SN - 1058-0468
SN - 1573-7330
ER -