{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T00:03:35Z","timestamp":1770681815542,"version":"3.49.0"},"reference-count":31,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Singapore Ministry of Health","award":["HSDP 05\/X01"],"award-info":[{"award-number":["HSDP 05\/X01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Spinocerebellar ataxia type 3\/Machado\u2013Joseph disease (SCA3\/MJD) is a neurodegenerative disorder caused by the ATXN3 CAG repeat expansion. Preimplantation genetic testing for monogenic disorders (PGT-M) of SCA3\/MJD should include reliable repeat expansion detection coupled with high-risk allele determination using informative linked markers. One couple underwent SCA3\/MJD PGT-M combining ATXN3 (CAG)n triplet-primed PCR (TP-PCR) with customized linkage-based risk allele genotyping on whole-genome-amplified trophectoderm cells. Microsatellites closely linked to ATXN3 were identified and 16 markers were genotyped on 187 anonymous DNAs to verify their polymorphic information content. In the SCA3\/MJD PGT-M case, the ATXN3 (CAG)n TP-PCR and linked marker analysis results concurred completely. Among the three unaffected embryos, a single embryo was transferred and successfully resulted in an unaffected live birth. A total of 139 microsatellites within 1 Mb upstream and downstream of the ATXN3 CAG repeat were identified and 8 polymorphic markers from each side were successfully co-amplified in a single-tube reaction. A PGT-M assay involving ATXN3 (CAG)n TP-PCR and linkage-based risk allele identification has been developed for SCA3\/MJD. A hexadecaplex panel of highly polymorphic microsatellites tightly linked to ATXN3 has been developed for the rapid identification of informative markers in at-risk couples for use in the PGT-M of SCA3\/MJD.<\/jats:p>","DOI":"10.3390\/ijms25158073","type":"journal-article","created":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T15:47:32Z","timestamp":1721836052000},"page":"8073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Preimplantation Genetic Testing of Spinocerebellar Ataxia Type 3\/Machado\u2013Joseph Disease\u2014Robust Tools for Direct and Indirect Detection of the ATXN3 (CAG)n Repeat Expansion"],"prefix":"10.3390","volume":"25","author":[{"given":"Mulias","family":"Lian","sequence":"first","affiliation":[{"name":"Preimplantation Genetic Diagnosis Centre, Department of Obstetrics and Gynaecology, National University Hospital, Singapore 119074, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6070-2333","authenticated-orcid":false,"given":"Vivienne J.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riho","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingjue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gui-Ping","family":"Phang","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2772-2583","authenticated-orcid":false,"given":"Arnold S.","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuling","family":"Liu","sequence":"additional","affiliation":[{"name":"KKIVF Centre, Reproductive Medicine, KK Women\u2019s & Children\u2019s Hospital, Singapore 229899, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4323-3635","authenticated-orcid":false,"given":"Caroline G.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore"},{"name":"Duke-NUS Medical School, Singapore 169857, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1872-5937","authenticated-orcid":false,"given":"Samuel S.","family":"Chong","sequence":"additional","affiliation":[{"name":"Preimplantation Genetic Diagnosis Centre, Department of Obstetrics and Gynaecology, National University Hospital, Singapore 119074, Singapore"},{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore"},{"name":"Molecular Diagnosis Centre, Department of Laboratory Medicine, National University Hospital, Singapore 119074, Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,24]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Amemiya, A. 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